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Fast-forward: the fourth dimension in development

Fast-forward: the fourth dimension in development Development 138 (24) BOOK REVIEWS 5269 multiple experimental fields. By contrast, An introduction to most models in mathematical biology are developed ad hoc to describe a single series mathematical biology of experiments. To think that a slim textbook could capture the entirety of Lance Davidson mathematical biology, with all its ad hoc models, would be absurd, but this book Bioengineering and Developmental Biology, Biomedical provides a good introduction to it by Science Tower 3, Room 5059, 3501 Fifth Avenue, University presenting classical applications of ODEs. of Pittsburgh, Pittsburgh PA 15260, USA. The first half of the book introduces the lad43@pitt.edu reader to the mathematical tool kit needed to doi:10.1242/dev.066977 formulate models and to solve or Mathematical Models of Biological problem in a way that allows equations to be characterize their behavior. Most of the Systems written which capture those details. For second half focuses on specific applications instance, we can distil the interactions of modeling, with chapters on population By Hugo van den Berg between predators and prey by stating the growth (ecology), dynamics of disease in Oxford University Press (2010) 256 pages ISBN 978-0-19-958218-1 (paperback), 978-0-19- rules that govern their populations. Rules populations (epidemiology) and within the 958219-8 (hardback) that govern the population of prey might individual (immunology), and physiology. £27.50/$49.50 (paperback), £65/$117 (hardback) include sources of population growth, such Many of the examples are similar to One of the key goals of modern cell and as birth or migration, and losses to the those found in classical texts, such as developmental biology is to expose the population due to predation or disease. James Murray’s series on Mathematical underlying principles that drive cell The precise statement of these rules Biology (Murray, 2007), Leah Edelstein- differentiation and to elucidate how should be complete enough to govern the Keshet’s Mathematical Models in Biology organisms construct functional multicellular mathematical formulation of the model. (Edelstein-Keshet, 2005) or Lee Segel’s structures. Thanks to advances in Given a well-defined word model, the excellent Modeling Dynamic Phenomena in sequencing, high throughput screens and mathematical biologist can then write a Molecular and Cellular Biology (Segel, sophisticated imaging technologies, these series of ODEs; for example, with variables 1984). Despite some organizational flaws, fields are now awash with quantitative that represent the number of predators and such as the placement of a chapter on the descriptions of gene transcription, cell prey and equations to describe how philosophy of mathematical modeling in the signaling and cell mechanics. However, populations of predators and prey change. middle of the book, and the introduction of extracting key principles from the flood of As students, we sometimes discovered that stochastic processes at the end of the book, new data is a major challenge for there were closed form solutions of these developmental biologists may be interested researchers and a central obstacle to ODEs, in which changes in variables can be in using van den Berg’s book to explore the fundamental progress in cell and predicted explicitly by equations. But more basic principles of mathematical modeling; developmental biology. The tools required often we found that we could only evaluate to interpret this vast amount of biological the general dynamic behavior of the A glaring omission from data and to test hypotheses based on these variables; for instance, whether populations studies can be found in quantitative analysis of predators and prey are stable or not. The this book is any discussion and mathematical modeling. With the book insights and training that these model- of pattern formation or ... Mathematical Models of Biological building exercises gave us were Systems, Hugo van den Berg aims to instrumental in becoming fluent in the basic diffusion-reaction contribute to the training of a new skills of mathematical modeling. The equations generation of biologists and mathematicians processes of formulating a model and and to provide them with an introduction to relating fundamental principles to the the methods that are now available to mathematics and experimental outcomes for example, for developing word models quantitatively analyze biological data. were often more informative than the and methods for solving and analyzing Like many quantitative biologists, my solution itself. However, after marveling at systems of ODEs. From the perspective of a first exposure to mathematical modeling the awesome power of ODEs, we soon developmental biologist, a glaring omission was not in the context of cell biology or realized that the solution of some, or indeed from this book is any discussion of pattern developmental biology, but came through most sets of, ODEs was intractable, that formation or examples of diffusion-reaction examples from physical chemistry, there was no way to capture relevant details equations. Early work on partial differential physiology and population ecology. In these of complex biology with continuous equations and pattern formation by Alan fields, simple problems can be formulated variables, or that model predictions could Turing in the 1950s (Turing, 1952) and Hans using ordinary differential equations not be tested experimentally. As such, the Meinhardt in the 1970s (Gierer and (ODEs) with complete statements of the tool kit of ODEs used to learn the skills of Meinhardt, 1972; Meinhardt, 1977) provided state variables, such as initial conditions. As mathematical modeling is less useful for the stimulus for many theorists to enter the students, we learned to write ‘word-models’ developing the quantitative models that are field of developmental biology and attracted and to translate these into sets of ODEs. needed to describe problems in cell and quantitative biologists to challenge those Word models are narrative passages developmental biology. models. Given the lack of textbooks focused intended to translate the details of a Unlike physics or chemistry, biology has on mathematical models in developmental biological problem such that biologists and very few universal theories. In classical biology, students interested in modeling the mathematicians alike can understand the physics, theoretical frameworks can connect complex problems of modern cell and DEVELOPMENT 5270 BOOK REVIEWS Development 138 (24) developmental biology would be well biology. However, more advanced students there seems to be no other way to understand advised to augment this text with other books and quantitatively inclined developmental the mechanisms underlying developmental on modeling specific biophysical systems biologists will have to wait for textbooks that processes than to know, at the descriptive and with more targeted reading of extensive provide a more complete introduction to level, how an organism undergoes normal supplemental materials that accompany the computational tools that have seen extensive development. Chapter 2 focuses on primary literature of gene regulatory application in recent years. Drosophila development, appropriately networks, cell signaling and morphogenesis. because, as the authors point out, we have References Current state-of-the-art modeling efforts in more in-depth developmental knowledge Edelstein-Keshet, L. (2005). Mathematical Models developmental biology range from Bayesian in Biology (Classics in Applied Mathematics). New about the fly than about any other animal. York: Society for Industrial and Applied models to finite element models to agent- The treatment is systematic and clearly Mathematics. based models, but the model-building presented, with beautiful illustrations. Most Gierer, A. and Meinhardt, H. (1972). A theory of exercises and focus on ODEs presented in of the important concepts are presented here; biological pattern formation. Kybernetic 12, 30-39. Meinhardt, H. (1977). A model of pattern formation van den Berg’s text are still essential to form although, not surprisingly in a text of limited in insect embryogenesis. J. Cell Sci. 23, 117-139. an understanding of the field of mathematical size, much of the crucial evidence is not. It is Murray, J. D. (2007). Mathematical Biology: I. An modeling in biology. The tutorial forms a justifiable way to present material to the Introduction. New York: Springer. Segel, L. A. (1984). Modeling Dynamic Phenomena presented by van den Berg provide a concise student, presumably providing reinforcement in Molecular and Cellular Biology. New York: introduction to the principles of modeling for lecture material, but leaving the lecturer Cambridge University Press. and dynamical systems and are suitable for something of substance to talk about. Some Turing, A. M. (1952). The chemical basis of an introductory course in mathematical morphogenesis. Phil. Trans. Roy. Soc. B 237, 37-72. might argue that the descriptions of concepts don’t matter a whit, and what is more important is that the students can reason and can design or interpret experiments to establish for themselves how a concept is We hold these principles to established. The ideal probably lies in between. Perhaps in a book about principles, be self-evident the authors could have put more emphasis on some of the general principles of Richard Harland developmental biology experiments, such as the inferences that can be drawn from University of California-Berkeley, 163 Life Sciences gain- and loss-of-function experiments, Addition #3200, Berkeley, CA 9472, USA. approaches which enjoy so many variations. harland@berkeley.edu The boxes that include the methods are doi:10.1242/dev.069864 generally excellent, though they are not Principles of Development illustrated in later chapters with examples necessarily presented in a consistent manner: from real animals and plants. The principles The Cre-lox system in the mouse and By Lewis Wolpert and Cheryll Tickle and concepts could be re-stated more mutagenesis in the fish receive nice pink Oxford University Press (2011) 656 pages ISBN 978-0-19-954907-8 forcefully throughout the book, though, as boxes, but homologous recombination in £36.99 (paperback) they may be missed by the inattentive embryonic stem cells is in line with the text. reader. Along the way, boxes explain the The latter techniques are described in the What is to be taught in an undergraduate important experimental techniques that chapters on vertebrate development. An course on developmental biology? As in all provide approaches to questions. The introductory chapter to this section branches of biology, there is far too much figures are drawn in a consistent style, describes vertebrate development and known to be able to teach it all, and any which helps to give a coherent presentation common methods, and is followed by a introductory course would sacrifice depth. and lets the student focus on content. chapter on setting up the body axes. This Inevitably, choices must be made, and one Although the images are variants of the represents a change from the previous choice is to emphasize important principles kinds of drawings we have seen in original edition, in which these topics were covered and concepts of development across all journal articles and other textbooks, they are in a single chapter, and is one of the good organisms. Lewis Wolpert and Cheryll rendered here with style and clarity. The updates. The chapters on vertebrate Tickle, with a cast of impressive supporting photographs are usually well chosen, though development, just like the others, are clear authors, have made excellent selections in in some cases they don’t seem to be as clear and beautifully written and illustrated. Principles of Development. This is the or as relevant as they should be. For Chapters covering the more complex topics, fourth edition of the book and the thoughtful example, it isn’t clear why a well- such as somite and nervous system choice of topics that went into the first camouflaged California false hellebore, the development, follow as epigenesis edition is still evident, although there have source of the teratogen cyclopamine, is proceeds. At this juncture, the early also been many useful updates. shown, rather than the (admittedly grisly) embryology of other prominent model The book begins with some history and a cyclopic consequences of its action. animals, the nematode, sea urchin and summary of general concepts. The concepts Once the concepts are dealt with, the book ascidian, take center stage, and a chapter on are important ones, especially when framed goes justifiably into detail on different plant development rounds out the coverage by the title of the book, but they may be a organisms. It is difficult to grasp general of organisms. little dry out of the context of real concepts without knowing the descriptive The book then circles back to various organisms. However, one has to start background; although the plethora of terms developmental processes. Admirable somewhere, and the general concepts are and structures may be daunting to the student, examples from various phyla are used to DEVELOPMENT Development 138 (24) BOOK REVIEWS 5271 illustrate the process of morphogenesis, in figures that would clarify the molecular should be principles of development – after which underlying cellular processes can be mechanisms at play in threshold activation. all, evolution selects whatever process seen to give rise to changes in the shape of Later in the book, one might have expected happens to work and developmental biology the organism or tissue. The selection of a deeper treatment of hedgehog signaling is full of ad hoc solutions to problems. examples from diverse organisms is made and threshold responses, as that might be the Nevertheless, there are some core principles possible by the earlier descriptive coverage, clearest case of a morphogen gradient at that recur in development, suggesting that which no longer need get in the way of the work in vertebrates. And what these must be either ancient and inherited, or discussion of concepts. Germ cells and sex is the best evidence that these molecules arrived at by convergence. Anterior- determination are followed by gene really act as morphogens? It certainly isn’t posterior patterning by deployment of Hox expression, cell differentiation and simple, but many students can deal with genes might be an example of the former, plasticity, including another excellent the evidence. Similarly, an important whereas branching morphogenesis might be update in the current edition – inevitably, on developmental principle is that internal an example of the latter, for which it is stem cells and the plasticity of gene organs achieve a high surface area by arguable that each organ might employ a expression. branching morphogenesis. The treatment different morphogenetic program. is again a bit glib; genes and proteins It is inevitable that a reviewer will raise that promote or inhibit branching are some criticisms; nevertheless, as it stands Lewis Wolpert and Cheryll enumerated, but I don’t think the authors this is an outstanding text with a well- can have stood up in front of a class and digested and comprehensive presentation of Tickle ... have made tried to argue that this really explains current views in developmental biology. It is excellent selections in branching, unless their students are more a text I can enthusiastically recommend for passive than ours. One hopes that the adoption in developmental biology courses. Principles of Development undergraduates will test the lecturer’s For those courses that have previously A book by Wolpert and Tickle would be understanding at points like this and demand used this text, is the fourth edition worth the incomplete without extended treatment of a deeper explanation, or an admission that upgrade? The hardback edition is expensive the limb, and a chapter on organogenesis the emperor indeed has no clothes. and it would be hard to justify the burden of includes vertebrate and insect limbs, eyes Finally, although the opening chapter an expensive new edition on a fresh set of and various internal organs. The authors’ addresses what may be some important undergraduates when the cheaper previous expertise in limb development is reflected principles and concepts, these should be editions of Principles of Development might in the greater citation of experiments in this more explicitly re-stated throughout the be available. The paperback is a better deal area, though this may challenge the book. I don’t think that students find these and my review copy hasn’t fallen apart yet. undergraduate who wants a clear-cut story. concepts obvious, particularly when the Still, as Oliver Wendell Holmes said, “A One has to admire Wolpert for giving details, terms and descriptions come thick man is usually more careful of his money prominent treatment to his progress zone and fast. Indeed, one might ask why there than of his principles.” model, which most people might present as a great idea that is no longer tenable. But, perhaps if a book is to emphasize principles, it only matters if they are good Fast-forward: the fourth possibilities, not whether they are currently supported. dimension in development The book closes with an excellent summary of developmental neurobiology, a Elaine Dzierzak* and Catherine Robin chapter on post-embryonic growth and development, an expanded treatment of Erasmus MC, Erasmus Stem Cell Institute, Dept of Cell regeneration and a good evo-devo summary. Biology, P.O. Box 2040, 3000 CA Rotterdam, The If the book is to remain manageable in Netherlands. size, it is inevitable that some favorite topics *e.dzierzak@erasmusmc.nl of the reader might be glossed over. doi:10.1242/dev.066969 However, despite the admirable emphasis on principles and concepts, I occasionally Imaging in Developmental Biology: embryo, from the zygote to gastrulation, to felt short-changed. With these authors, I A Laboratory Manual organogenesis, and birth, has been a subject might have expected a deeper treatment of of fascination and science (fiction?) for Edited by James Sharp and Rachel O. Wong what surely must be one of the most centuries. This fascination is reflected in the Series Editor, Rafael Yuste important principles: the existence of many historical drawings of developing Cold Spring Harbor Laboratory Press (2011) 883 Pages threshold responses to morphogens – embryos and by advances in the field of ISBN 978-0-879699-40-6 (paperback), 978-0- molecules that diffuse from a source and set embryology that came with the invention of 879699-39-0 (hardback) $165 (paperback), $246 (hardback) up a graded concentration. Instead, when it the microscope. With the aid of microscopy, gets to the nitty gritty of boundaries, the the field advanced from drawings of activating and repressing activities of one Development is a bit like Star Trek, the embryos to static images of fixed sections, gradient (such as hunchback or dorsal) are long-running television series in which which could be rendered, with some mental mentioned, but how one protein both ‘space’ is the final frontier. For effort, into three-dimensional (3D) activates and represses is not explained. development, the final frontier is the fourth structures. However, comparisons of Indeed, the text gets pretty dense and lacks dimension, ‘time’. Time travel through the embryos at different formative stages could DEVELOPMENT 5272 BOOK REVIEWS Development 138 (24) only hint at the patterns of dynamic cell provided on embryo accessibility and size, groups of cells. The excellent figures and growth and morphological change that tissue transparency, different cell-marking descriptions that detail how to culture occur during development, which recent techniques, phototoxicity, mounting embryos, hold them in place and manipulate molecular and genetic analyses have begun methods and compatibility with imaging them will be of great use for studying cell- to uncover. Importantly, the current resolution, and image analysis. Chapters fate determination and migration in early advances being made in innovative, real- are written by experts in the field, and each mouse development. Chapters 19 and 23 time imaging technologies and in the starts with a brief introduction into the describe the imaging of embryo slice computational processing of images have mechanisms of development being cultures in various species and tissues. As an now fast-forwarded the field boldly into the addressed and with a description of the important aspect of neural development, the dynamic fourth dimension. These advances specific imaging method used, followed imaging of circuit formation is the focus of are now summarized and explained in a by one or more protocols. Concise Chapters 24-35, which are aimed at newly published book on imaging, Imaging troubleshooting, discussion, recipes, web specialists studying neuron excitation, in Developmental Biology, edited by James resources and reference sections provided axon pathfinding or synapse formation. Sharp and Rachel O. Wong, both experts in at the end of each chapter are of added However, these approaches are also of this field. benefit in ensuring the success of the broader relevance to research in other approach. developmental systems. Live imaging of cells is the focus of Imaging multicellular tissues and organs It is a valuable guide ... Section 2. Cell-labeling protocols in as a whole dynamic entity is covered in Chapters 8-13 provide an extensive Section 3. The first two chapters (Chapters 36 although serious training coverage of dye injection and and 37) explain how to quantify morphogen might be required to electroporation techniques for groups of, gradients over time in Drosophila embryos. and for single, cells in chick, mouse, We found these chapters harder to understand perform the more Xenopus and zebrafish embryos. The and aimed more at the specialist reader. By complex experiments protocols provide important technical contrast, Chapters 38-43 on cell movement details about, for example, injection pipette describe more commonly used methods to Imaging in Developmental Biology is an production, electrode placement, voltage acquire high-resolution dynamic movies of excellent resource from which both novices strength, pulse duration and intervals. Other cells or subcellular proteins during and experienced researchers can obtain labeling techniques covered include the morphogenesis in Xenopus, zebrafish, chick, current state-of-the-art embryo-imaging difficult MARCM (mosaic analysis with quail and mouse embryos. Protocols protocols for studying key developmental repressible cell marker) in Drosophila and provided in this section include how to events, such as cell-fate determination, MADM (mosaic analysis with double generate Xenopus and zebrafish embryos morphogen gradient formation, cell-cell marker) in mice. Commonly used direct with mosaic fluorescent reporter expression interactions, cell migration and transgenesis and knock-in strategies with and how to prepare and mount tissue explants morphogenesis. The eye-catching cover fluorescent marker genes, as well as Cre- or whole embryos for long-term imaging, immediately attracted passing lab members, Lox recombination and fluorescence- together with useful troubleshooting tips. encouraging them to browse the book, photoactivation methods, are presented in This section also contains a well-illustrated which they did with increasing interest. the context of specific developmental protocol to perform high-resolution The first comment often expressed was: questions concerning cell-lineage tracing. multiphoton time-lapse imaging of a “I did not know that we could do so much!” The relative merits of the different strategies developing chick embryo and protocols Upon first perusal, this comprehensive are clearly described in Chapter 13. for 3D time-lapse imaging of epithelial book seems almost overwhelming with Chapters 14-23 cover live cell imaging of morphogenesis and of the mouse an impressive 57 chapters and seven cell migration, mostly of the neuronal metanephric kidney. Two relatively new appendices. But it does contain just about system. Particularly useful here are the imaging technologies are presented in everything known about imaging embryos. descriptions of the use of the Chapters 44-46 that allow live imaging of This is not surprising as the volume is based, photoconvertible fluorescence marker developing whole embryonic organs – in part, on the popular and excellent Cold Kaede to study neuron birth dating in optical coherence tomography (OCT, an Spring Harbor imaging course. The editors zebrafish embryos, and the explanation of optical version of ultrasound used to have organized the book into four large DNA injection methods, embryo image high-speed events) and a non-invasive sections, which contain chapters that embedding, image acquisition and software ultrasound technology used to image are frequently and conveniently cross- usage in the context of studies of zebrafish 3D organ geometry (which allows referenced. A particularly helpful table is retina and lateral line development. As developmental events to be imaged over provided in Chapter 1 that guides the reader mouse developmental biologists, we found time). to specific protocols of interest in different the zebrafish protocols and figures (in After single cells and organs, Section 4 animal models. Chapters 16-18) easy to understand. Of focuses on imaging the whole embryo in 3D Section 1 (Chapters 1-7) provides a special interest to us were Chapters 20 and and 4D. These chapters provide detailed general entry into the imaging of common 21, as the details of pre- and post- protocols for the collection of spatial and model organisms. This section’s emphasis gastrulation mouse embryo dissections with temporal patterns of gene expression, for on the advantages and disadvantages of excellent accompanying figures are an embryo phenotyping and for generating each model organism allows researchers to important resource for our students. These static or dynamic 3D atlases of model evaluate quickly which animal model and chapters contain detailed protocols for systems. Of particular interest is Chapter 48, procedures might be most useful for their tagging cells with dyes, grafting cells into which provides a didactic description of specific investigations. Information is embryos and for electroporating DNA into the intellectual and technical efforts of DEVELOPMENT Development 138 (24) BOOK REVIEWS 5273 the Berkeley Drosophila transcription particular interest to developmental ways in which gene expression is regulated network project, which has produced biologists. post-transcriptionally, have meant that the a computationally analyzable, gene Altogether, Imaging in Developmental field of RNA has undergone rapid growth in expression and morphological 3D atlas Biology is a book for those Development the past few decades. This rapid growth has of a blastoderm embryo. The use of readers who are curious to know more recently increased even further because of hardware and software is also well about new technical developments and the discovery of RNA interference (RNAi), explained and illustrated in detail, including possibilities within the exciting field of as well as the discovery that small RNAs, chapters on optical projection tomography imaging. It is a valuable guide and a very distinct from tRNA and snRNA, undergo (OPT), X-ray micro-computed tomography helpful laboratory manual for students, processing to fulfil a range of cellular (mCT), episcopic fluorescence image although serious training might be required functions. These include the regulation of capturing (EFIC), high-resolution episcopic to perform the more complex experiments. transposable element transposition by microscopy (HREM) and macroscopic Seven appendices at the end of the book are piRNAs, regulation of translation by magnetic resonance imaging (mMRI), with particularly helpful for new people entering microRNAs and still poorly explored large detailed information again provided for the field and include a must-have list of non-coding RNAs (ncRNA). Many of these troubleshooting as well as additional web fluorescent filters and excitation/emission ncRNAs have turned out to have important resources. Descriptions of the advantages, spectra, lens cleaning tips, a list of cautions roles in development and during disease disadvantages, limitations and future and potential disasters, and an all-important processes, such as cancer. Therefore, it is prospects of each technique will definitely glossary of terms. The book is pleasant to clear that all aspects of RNA molecular assist readers in choosing the appropriate read, with its clever use of illustrations, biology have now become central to our method for their own application. The photos and online protocol videos. Thus, understanding of cell and developmental fourth dimension, time, is finally reached in we highly recommend this book and biology. the last chapters (56 and 57). Protocols are hope that multidisciplinary collaborative Despite the rapid growth and exciting provided here for high-volume 3D time- expertise in biology, imaging, image discoveries made recently in the field of lapse imaging of live adult Caenorhabditis analysis, computer science, visualization RNA, to my knowledge there has not elegans and of zebrafish and Drosophila and database construction will continue to been a comprehensive textbook for embryos. Digital representations of these fast-forward 4D imaging techniques and, undergraduates and postgraduate students embryos permit cell tracking in time, consequently, our knowledge of that focuses on the molecular biology of revealing their origin and fate, which is of development. the cell from the perspective of RNA. Molecular Biology of RNA, by David Elliot and Michael Ladomery, now plugs this gap. This comprehensive textbook is pitched at just the right level and explains A molecular view of the life the concepts in sufficient detail to make them come to life without swamping the and time of RNA uninitiated with confusing information and jargon. The authors have to be Ilan Davis congratulated on the comprehensive nature of the textbook, which means that even Department of Biochemistry, The University of Oxford, RNA aficionados will find useful South Parks Road, Oxford OX1 3QU, UK. information within its pages. At the same ilan.davis@bioch.ox.ac.uk time, it is a relatively short tome (400 or so doi:10.1242/dev.067033 pages) and reasonably priced. Molecular Biology of RNA now regarded to have credible catalytic After introducing some important properties through the availability of its 2- general principles of RNA structure, By David Elliot and Michael Ladomery OH, a reactive group that replaces a non- catalysis and RNA-binding proteins, the Oxford University Press (2010) 460 pages ISBN 978-0-19-928837-3 reactive ‘O’ atom in DNA. Moreover, its chapters of the book are structured £34.99/$55 (paperback) catalytic roles include key functions in the according to the life cycle of an mRNA, most important molecular machines of the starting with its birth in the nucleus, its Following the discovery of the structure of cell, such as the spliceosome and ribosome. splicing and processing and exit from the DNA and during the early days of molecular In hindsight, it would perhaps not be so nucleus, and moving onto its subsequent biology, RNA was considered to be a less surprising if the RNA world hypothesis cytoplasmic localisation, translation and interesting cellular component to study than turned out to be correct. This hypothesis degradation. These broad themes are DNA. This was primarily because RNA states that the first life forms on our planet broken down into more detailed concepts; was thought to be simply a molecular were RNA-based simple cells in the pre- for example, RNA processing is covered photocopy of the genetic blue print stored biotic soup. RNA is certainly a better by chapters on co-transcriptional in DNA. But how things have changed! candidate than either DNA or proteins for a processing, splicing, alternative splicing, Since those early days, our understanding of self-replicating molecule that acts both as a and splicing defects in development and the cellular roles of RNA has changed template for, and that has the necessary disease. Nuclear exit is broken down radically. RNA is now considered to be of catalytic machinery to perform, its own into the processes of mRNA central importance to both molecular replication. Moreover, the discovery that nucleocytoplasmic trafficking and ncRNA biology and cellular function. Far from only most mRNAs are spliced, and the gradual nucleocytoplasmic trafficking. It is clear containing genetic information, RNA is uncovering of a breathtaking number of that the authors have placed greater DEVELOPMENT 5274 BOOK REVIEWS Development 138 (24) emphasis on nuclear events than on those Although Molecular Biology of RNA cytoplasm, such as mRNA localisation, in the cytoplasm. Although this makes the offers a good systematic introduction to RNA translation and degradation. I am already textbook a little unbalanced, it does mean research, it is also important to consider the looking forward to the next edition, in which that for anyone interested in nuclear events limitations of the book. The diagrams are these deficiencies can be addressed, perhaps related to RNA, there is considerable perhaps a little too simplistic and would at the expense of making the textbook a little detail. By contrast, for topics like mRNA certainly have benefited from a more stylised longer and increasing its cost slightly. localisation, the book offers a simplified approach and perhaps from being in colour. References overview to less experienced scientists, However, this may have pushed up the cost Atkins, J. F., Gesteland, R. F. and Cech, T. R. but lacks necessary details. of the textbook. As mentioned earlier, (2010). RNA Worlds: From Life’s Origins to Diversity in Gene Regulation. New York: Cold Spring Harbor perhaps most importantly, there is an over- Laboratory Press. representation of events in the nucleus, This comprehensive Darnell, J. E. (2011). RNA: Life’s Indispensable particularly splicing, at the expense of Molecule. New York: Cold Spring Harbor textbook is pitched at just equivalent levels of detail on topics in the Laboratory Press. the right level and explains the concepts in sufficient detail to make Epigenetics in all its glory them come to life 1,2 Mellissa R. W. Mann The book is well written, easy to follow Department of Obstetrics & Gynaecology and and, on the whole, strikes a good balance Department of Biochemistry, Schulich School of Medicine between providing sufficient detail and and Dentistry, University of Western Ontario, London, providing a simplified description of Ontario, Canada N6A 5W9. Children’s Health Research complex concepts. The authors have Institute, London, Ontario, Canada N6C 2V5. succeeded in producing a volume that is mmann22@uwo.ca very useful for both undergraduate and doi:10.1242/dev.069989 graduate students starting a research career in an RNA-related topic, as it includes a Epigenetics methylation, histone modifications, changes comprehensive glossary at the end of the Linking Genotype and Phenotype in in chromatin structure, and effects of non- book. The textbook will still be of value Development and Evolution coding RNAs. This book includes five to more experienced researchers from chapters on molecular epigenetics, covering Edited by Benedikt Hallgrímsson and Brian K. Hall other fields that wish to get a quick various organisms and topics from asexual comprehensive introduction to RNA University of California Press (2011) 472 pages organisms in the study of epigenetic ISBN 978-0520267091 (hardback), 978-0520948822 research or to get started with a particular variation to epigenetics and human disease. (eBook) subtopic, such as splicing or mRNA One chapter highlights neural development £59/$68 (hardback), $85 (eBook) localisation, as each section has a well in which cell-fate switches are intimately chosen set of references as an entry point Ask ten scientists their definition of linked with epigenetic changes. For to a field. When deciding whether to epigenetics and you may get ten answers. In example, transition from a neural stem cell purchase the book, readers may wish to its simplest form, epigenetics can be defined to a progenitor cell involves a switch in co- consider what else is available covering as above (epi) the level of genes (genetics), factor associations. In response to Notch the topic of RNA. There are a number of and in the book entitled Epigenetics: effector molecules, the HES1 repressor other excellent textbooks that focus on Linking Genotype and Phenotype in complex is transformed into a HES1 methods used in the RNA field; for Development and Evolution, the editors, activator complex, thereby inducing a example, RNA Worlds: From Life’s Benedikt Hallgrímsson and Brian K. Hall, progenitor cell fate. A different mechanism Origins to Diversity in Gene Regulation. have assembled 23 chapters that collectively may be utilized in neuronal fate In general, these textbooks are more embody epigenetics as described by this specification in the neocortex. Changes in specialised, more expensive and appeal to broad definition. Although the book is DNA looping and nuclear matrix binding more experienced researchers. This year organized into four parts, it can be distilled may specify an upper layer neocortical fate. has also seen the publication of RNA: into three themes that each discusses a This chapter describes the current Life’s Indispensable Molecule by James more detailed interpretation of the field: understanding of various epigenetic Darnell, which, like the textbook by Elliot molecular epigenetics, classical epigenetics/ mechanisms involved in neural cell fate and Ladomery, is also being sold at an epigenetic interactions, and epigenetic decisions. affordable price and is also meant for interactions and evolution. The second theme of the book is young researchers at the beginning of their In its modern molecular reiteration, classical epigenetics or epigenetic research careers. However, Darnell uses a epigenetics is defined as a change in gene interactions. It is referred to as classical very personal and subjective style to activity without a change in DNA sequence. because the term ‘epigenetics’ was first describe the history of RNA research – a Most molecular definitions of epigenetics coined by Conrad Waddington in 1942. very different approach from the also include the idea of heritability, or Waddington’s definition of epigenetics was systematic textbook description employed memory of gene activity, through cell ‘the branch of biology which studies the by Elliot and Ladomery in Molecular division. Here, epigenetic modifications causal interactions between genes and their Biology of RNA. modulate gene expression through DNA products which bring the phenotype into DEVELOPMENT Development 138 (24) BOOK REVIEWS 5275 being’ (Waddington, 1942). In Chapter 7, have evolved long snouts with upturned these definitions of epigenetics is the Ellen Larsen and Joel Atallah introduce mouths suitable for planktonic prey, have complex and finely tuned choreography of epigenesis as the gradual unfolding of lost group cannibalistic behaviour and development. In the not too distant future, structure and function during development display conspicuous courtship displays. In we will probably find that these definitions and present the analogy of a fertilized hen’s shallow, nutrient-rich lakes, threespine are intimately linked. As stated by Root egg that develops into a downy chick: sticklebacks have short snouts and wide Gorelick, Manfred Laubichler and Rachel scrambling the egg retains all the genetic mouths for feeding on benthic invertebrates, Massicotte in Chapter 6 ‘the molecular material and yet there is no development. display group cannibalistic foraging and epigenetic signals [can be considered] the This exemplifies the point of epigenetic have inconspicuous courtship, consisting nuts and bolts underlying the classical interactions that occur above the gene of dorsal pricking. This chapter explores epigenesis sensu Waddington’. level. Here, epigenetic interaction is the the phenotypic plasticity of an ancestral This book celebrates epigenetics in all umbrella term for cell migration, physical population in response to novel its glory. As a first of its kind, I recommend interaction among cells and tissues, environments and its role in influencing this book to researchers and graduate mechanical forces, embryonic induction subsequent evolutionary change. students who want to widen their (including cell signalling and hormones), In all languages, including the language perspective of epigenetics and its role in and interactions between cells and their of biology, words and terms can evolve and, development and evolution. Because of the intrinsic or extrinsic environment. All thus, their meaning can change. Over time, division in meaning, this book does require these interactions may play a role in the modern molecular definition of the reader to switch gear depending on generating the ‘epigenetic landscape’ ‘epigenetics’ has supplanted other whether the chapter is on molecular or through which a cell must transverse to definitions. In Epigenetics: Linking classical epigenetics. Furthermore, it is reach its final differentiated state within Genotype and Phenotype in Development steeped in epigenetic, development and a tissue or organ. These epigenetic and Evolution, Hallgrímsson and Hall evolution terminology. This makes it less interactions are discussed in nine chapters, provide a comprehensive selection of than suitable for the undergraduate student. each of which focuses on the development epigenetics in its many forms and appeal to However, this book would be an excellent of a specific cell type, tissue or organ. One the reader to accept a broader definition of resource for a graduate course in classical chapter describes the mechanical force of epigenetics – one that includes all things epigenetics, or epigenetic interactions and muscle activity on bone as an epigenetic epigenetic: not just molecular epigenetics, evolution. stimulus for developmental change. Using but also classical epigenetics and epigenetic Reference the mammalian jaw as the model system, interactions related to evolution. Waddington, C. H. (1942). The epigenotype. the effects of mechanical force (muscle Importantly, the context inherently linked in Endeavour 1, 18-20. force, bite force and compression load) on lower mandible condylar cartilage growth are explored. Evidence is presented for increasing force leading to shorter, wider A wake-up call to delve condylar cartilage growth and decreasing force for longer, thinner condylar cartilage deeper into the cell growth. This chapter illustrates mechanical forces on development as an epigenetic Wendy A. Bickmore mechanism. MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh, Ask ten scientists their Edinburgh EH4 2XU, UK. definition of epigenetics W.Bickmore@hgu.mrc.ac.uk doi:10.1242/dev.067025 and you may get ten answers The Nucleus – transcription, replication, repair – occur. In developmental biology papers it is not Edited by Tom Misteli and David L. Spector The third theme, covered by six chapters uncommon to find a final summary figure in Cold Spring Harbor Laboratory Press (2011) 517 pages in this book, is epigenetic interactions as a ISBN 978-0-879698-94-2 which a signaling pathway ends up pointing $135 (hardback) framework for evolution. For example, one into an oval-shaped nucleus, devoid of any chapter focuses on the epigenetic integration structure or organization, save for a linear of various head modules (brain, Why should a developmental biologist be depiction of a target gene locus. However, the bone/cartilage, muscle, eyes, tongue, teeth, interested in a book about the nucleus? nucleus is not a homogenous space and muscles, sinuses/cavities) in development Almost 80 years ago, Conrad Waddington neither is the genome in its natural nuclear and its variations during human craniofacial put forward ideas about how gene products environment arranged in a linear fashion. evolution. Another chapter discusses the could regulate development. In modern The contributions in this book, from concept of adaptive plasticity and genetic parlance, much of development is the result international leaders in the field of nuclear assimilation in evolutionary change, as of the differential use of the same genome in organization and function, are based exemplified by the phenotypic and different cell types and at different upon the premise that we cannot really behavioural changes in threespine developmental stages within the same understand how genomes function without an sticklebacks in different ecotypes. In deep, organism. This originates in the nucleus, appreciation and understanding of their nutrient-poor lakes, threespine sticklebacks where the processes that act upon the genome natural cellular environment – the nucleus. DEVELOPMENT 5276 BOOK REVIEWS Development 138 (24) The 28 chapters are organized to provide There are several examples of proteins that They describe the amazing nuclear a comprehensive overview of nuclear are expressed within a particular cell reorganization of the genome that occurs, compartments and their components (e.g. type, but are sequestered into a nuclear after birth, in the rod cells of nocturnal nuclear membrane, nuclear pore complex, compartment that renders them functionally mammals and they emphasize how such a chromosome territories, Cajal body, inactive. Thoru Pederson gives a fascinating fundamental aspect of nuclear organization nucleolus), to discuss how this organization example of this (sequestration of the Hand1 can be turned on its head in the face of relates to function (transcription, DNA transcription factor into the nucleolus of selection pressure – in this case, to facilitate replication and repair, RNA processing) trophoblasts) in his chapter on the nucleolus. the passage of photons to photoreceptors in and to describe the defects in nuclear This should be a wake-up call for low light levels. organization in human disease. The focus is developmental biologists to delve deeper There are other equally fascinating primarily on the nucleus in mammalian into subcellular organization. Conversely, examples to be found in this book where cells, but there are also discussions on other most cell biology of the nucleus is still nuclear organization impinges directly simpler model organisms – budding yeast, studied in cell lines rather than in real on developmental processes. Nuclear Caenorhabditis elegans and Drosophila. biological organisms or embryos. There is condensation in terminally differentiated Each chapter is relatively short and clearly scope to bridge these two disciplines. cells and aberrant nuclear organization in accessible, making this a great resource to Indeed, in their chapter on Chromosome cancer are just two examples that come dip into. Illustrations are used sparingly but Territories, Thomas and Marion Cremer immediately to mind. So, although not are well chosen. provide a superb example of the benefits targeted at developmental biologists, if your The main target audience for this book that can come from considering nuclear interest in the nucleus is piqued, then this is likely to be teachers and students of organization in a developmental setting. book is a good place to start. cell biology. The most interest for developmental biologists will lie in those chapters that deal with the organization of the genome and the transcriptional A practical guide to human machinery within the nucleus. Spatial and temporal changes in genome organization stem cell biology are increasingly recognized as important aspects of gene regulation, especially in Neil Singh and Ludovic Vallier* stem cells and differentiation. Thus, from a developmental biologist’s perspective, it is The Anne McLaren Laboratory for Regenerative disappointing that no specific chapter is Medicine, Department of Surgery, University of dedicated to the nucleus in development, but Cambridge, Cambridge CB2 0SZ, UK. there are nuggets of relevant information *lv225@cam.ac.uk within most chapters. The chapter on dosage doi:10.1242/dev.067256 compensation (written by Jennifer Chow and Edith Heard) is of direct relevance to Human Stem Cell Technology and manageable and appropriate for a newcomer events that occur in early embryogenesis, Biology: A Research Guide and to the field or for an early career scientist and a chapter on Lamin-binding proteins Laboratory Manual working with human pluripotent cell lines for (written by Katherine Wilson and Roland the first time. Edited by Gary S. Stein, Maria Borowski, Mai X. Luong, Meng-Jiao Shi, Kelly P. Smith Foisner) emphasizes the fact that proteins of The editors are all based at the Center for and Priscilla Vasquez the nuclear periphery that link the nucleus to Stem Cell Biology & Regenerative Wiley-Blackwell (2011) 419 pages the cytoskeleton are particularly important Medicine at the University of Massachusetts ISBN 978-0-470-59545-9 in regulating the position of the nucleus in Medical School. The individual chapters are £93.50/€112.20 (hardback) specific cell-types or tissues (e.g. retina and written predominantly by scientists from neurons) and in relaying signals from the Do we need another book on human stem cell institutes on the East coast of the United cytoplasm to the nucleus. biology? The field is fairly long in the tooth States, although some contributors are based now, thirteen years after Thomson first in Australia, Canada and China. The book is derived human embryonic stem (ES) cells divided broadly into five sections: an No specific chapter is (Thomson et al., 1998). There are many introduction; two sections on the culture and dedicated to the nucleus books that cover the theoretical aspects of the characterisation of human pluripotent stem discipline (Oderico et al., 2004) and others cells; and two sections covering more recent in development, but there that attempt to collate protocols useful to technologies and applications relevant to are nuggets of relevant human stem cell biologists (Sullivan et al., human ES cells. 2007). Nevertheless, the new book Human In the introduction, the authors have information within most Stem Cell Technology and Biology succeeds managed to distil over 50 years of stem cell in combining both of these characteristics, advances in just a few pages of text. chapters providing not only a clear account of the Although this may be too short for Developmental biologists often ask scientific discoveries underpinning human experienced scientists hoping for a colourful where and when a gene or protein is stem cell biology, but also a useful range of narrative history of each breakthrough, we expressed in the developing organism. laboratory protocols. The end product may be think it does well to bring even novice However, rarely do they ask precisely where less comprehensive than Lanza’s classic text readers up to speed with current thinking in within the cell a particular protein is located. (Lanza et al., 2009), but it is perhaps more stem cell biology, from the bottom up. DEVELOPMENT Development 138 (24) BOOK REVIEWS 5277 References The sections containing protocols are (using stem cells or insights into growth Lanza, R., Gearhart, J., Hogan, B., Melton, D., excellent and provide the perfect conditions to help repopulate and regenerate Pedersen, R. A., Thomas, E. D., Thomson, J. A. framework for experimental work on degenerative and diseased organs). and Wilmut, I. (2009). Essentials of Stem Cell human stem cells. Each chapter is devoted Although brief, the final chapter manages to Biology. Maryland Heights: Academic Press. Odorico, J., Pedersen, R. A. and Zhang, S. (2004). to a separate technique and begins with an encapsulate the major recent breakthroughs Human Embryonic Stem Cells. Abingdon: Taylor & extremely helpful overview that underlines and future prospects for cell replacement Francis. the basic steps, and importance, of each therapies in ectodermal, mesodermal and Sullivan, S., Cowan, C. A. and Eggan, K. (2007). Human Embryonic Stem Cells: The Practical protocol. The layout has been well thought endodermal tissues. Handbook. Hoboken: Wiley-Blackwell. out, supplementing the customary One of the book’s major strengths is Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., ‘equipment’ and ‘procedure’ sections with the accompanying DVD. It provides Ichisaka, T., Tomoda, K. and Yamanaka, S. helpful tables, log sheets with blanks to be printable copies of the protocols from the (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell filled in and space for the reader to make book, and even has a helpful search tool, 131, 861-872. their own notes in the margin. These which we found extremely useful. The Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., protocols have been used as part of DVD also contains six videos, which Waknitz, M. A., Swiergiel, J. J., Marshall, V. S. and Jones, J. M. (1998). Embryonic stem cell lines practical courses in stem cell biology at the demonstrate good laboratory practice, derived from human blastocysts. Science 282, University of Massachusetts Medical aseptic technique and how to harvest, 1145-1147. School for several years, and this is evident passage and thaw cells. We would strongly by the careful explanation of each recommend that laboratories use these technique in the book and the thoughtful videos as part of the induction of new addition of pros and cons of each members to stem cell labs, as few laboratory Other recent books of interest technique. members have the time or training to offer Haldane, Mayr, and Beanbag Genetics By Krishna Dronamraju Later sections of the book will appeal to such a clear and standardised tutelage on the Oxford University Press (2011) 296 pages established stem cell investigators as they basics of laboratory practice and stem $34.95 (hardback) summarise the latest in bioinformatic, cell culture. The lead editor, Professor MicroRNAs in Development: Methods and genomic, epigenetic and proteomic Gary Stein, provides much of the training Protocols analyses of human stem cells. These in these videos himself. The book also Edited by Tamas Dalmay Springer (2011) 227 pages chapters provide a brief account of the boasts a student companion website £85.50 (hardback) logic and application of these various (http://www.wiley.com/go/stein/human) Developmental Biology, 9th edition techniques, and feature tables and pictorial which is supposed to collate updates, By Scott Gilbert representations of the scientific basis of the amendments and additional resources. Sinauer (2010) 711 pages techniques. This is most notable in the However, we were disappointed to discover $129.95 (hardback) chapter on epigenetics. that at the time of writing there were no Plant Transformation Technologies Edited by C. Neal Stewart, Jr, Alisher Touarev, Four years after Yamanaka’s group first additional resources available. Vitaly Citovsky and Tzvi Tzfira successfully reprogrammed differentiated Wiley-Blackwell (2011) 296 pages adult human dermal fibroblasts into £140 (hardback) To the beginner, the field pluripotent cells (Takahashi et al., 2007), The Dynamic Genome: A Darwinian much attention should be paid to the of stem cell biology ... can Approach By Antonio Fontdevila chapter devoted to reprogramming and Oxford University Press (2011) 232 pages seem impossible to induced pluripotent stem cells. It outlines £49.95 (hardback) the differences between reprogramming navigate. This book will RNA: Life’s Indispensable Molecule during fertilisation and during somatic cell By James E. Darnell act as an excellent guide. Cold Spring Harbor Laboratory Press (2011) 416 pages nuclear transfer. The chapter describes the $40 (hardback) major developments in reprogramming, Mechanisms of Life History Evolution such as the use both of cell extracts and of We would recommend this readable and Edited by Thomas Flatt and Andreas Heyland transcription factors, most notably the well-organised book to all laboratories Oxford University Press (2011) 504 pages Yamanaka factors: Oct4, Sox2, c-myc and dealing with human ES cells. We envisage £45 (paperback) Klf4. The chapter does well to highlight that a laboratory copy will prove to be Epigenetics: The Ultimate Mystery of the limitations of the current protocols, as invaluable as a reference text for all new Inheritance By Richard C. Francis well as recent attempts to improve the members of your laboratory, and the later W. W. Norton & Company (2011) 234 pages efficiency and safety of classical directed sections will be of benefit to more senior £19.99 (hardback) reprogramming using the Yamanaka investigators. Although not the most factors. energetic nor the most exhaustive book of Much has been made of the potential this type on the market, this volume applications of human stem cell biology. succeeds by summarising the historic and The final section deals with these recent research breakthroughs in human ES applications. These include the use of stem cell science and combining this with cells in drug screening (testing various types excellent and reliable laboratory protocols. and doses of medications to streamline To the beginner, the field of stem cell the drug development process); stem cells biology – with a burgeoning number of as in vitro models of disease (to principles, terms and techniques to master – further understanding of aetiology and can seem impossible to navigate. This book pathogenesis); and stem cells in cell therapy will act as an excellent guide. DEVELOPMENT http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Development The Company of Biologists

Fast-forward: the fourth dimension in development

Development , Volume 138 (24) – Dec 15, 2011

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The Company of Biologists
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© 2021 The Company of Biologists. All rights reserved.
ISSN
0950-1991
eISSN
0950-1991
DOI
10.1242/dev.066969
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Abstract

Development 138 (24) BOOK REVIEWS 5269 multiple experimental fields. By contrast, An introduction to most models in mathematical biology are developed ad hoc to describe a single series mathematical biology of experiments. To think that a slim textbook could capture the entirety of Lance Davidson mathematical biology, with all its ad hoc models, would be absurd, but this book Bioengineering and Developmental Biology, Biomedical provides a good introduction to it by Science Tower 3, Room 5059, 3501 Fifth Avenue, University presenting classical applications of ODEs. of Pittsburgh, Pittsburgh PA 15260, USA. The first half of the book introduces the lad43@pitt.edu reader to the mathematical tool kit needed to doi:10.1242/dev.066977 formulate models and to solve or Mathematical Models of Biological problem in a way that allows equations to be characterize their behavior. Most of the Systems written which capture those details. For second half focuses on specific applications instance, we can distil the interactions of modeling, with chapters on population By Hugo van den Berg between predators and prey by stating the growth (ecology), dynamics of disease in Oxford University Press (2010) 256 pages ISBN 978-0-19-958218-1 (paperback), 978-0-19- rules that govern their populations. Rules populations (epidemiology) and within the 958219-8 (hardback) that govern the population of prey might individual (immunology), and physiology. £27.50/$49.50 (paperback), £65/$117 (hardback) include sources of population growth, such Many of the examples are similar to One of the key goals of modern cell and as birth or migration, and losses to the those found in classical texts, such as developmental biology is to expose the population due to predation or disease. James Murray’s series on Mathematical underlying principles that drive cell The precise statement of these rules Biology (Murray, 2007), Leah Edelstein- differentiation and to elucidate how should be complete enough to govern the Keshet’s Mathematical Models in Biology organisms construct functional multicellular mathematical formulation of the model. (Edelstein-Keshet, 2005) or Lee Segel’s structures. Thanks to advances in Given a well-defined word model, the excellent Modeling Dynamic Phenomena in sequencing, high throughput screens and mathematical biologist can then write a Molecular and Cellular Biology (Segel, sophisticated imaging technologies, these series of ODEs; for example, with variables 1984). Despite some organizational flaws, fields are now awash with quantitative that represent the number of predators and such as the placement of a chapter on the descriptions of gene transcription, cell prey and equations to describe how philosophy of mathematical modeling in the signaling and cell mechanics. However, populations of predators and prey change. middle of the book, and the introduction of extracting key principles from the flood of As students, we sometimes discovered that stochastic processes at the end of the book, new data is a major challenge for there were closed form solutions of these developmental biologists may be interested researchers and a central obstacle to ODEs, in which changes in variables can be in using van den Berg’s book to explore the fundamental progress in cell and predicted explicitly by equations. But more basic principles of mathematical modeling; developmental biology. The tools required often we found that we could only evaluate to interpret this vast amount of biological the general dynamic behavior of the A glaring omission from data and to test hypotheses based on these variables; for instance, whether populations studies can be found in quantitative analysis of predators and prey are stable or not. The this book is any discussion and mathematical modeling. With the book insights and training that these model- of pattern formation or ... Mathematical Models of Biological building exercises gave us were Systems, Hugo van den Berg aims to instrumental in becoming fluent in the basic diffusion-reaction contribute to the training of a new skills of mathematical modeling. The equations generation of biologists and mathematicians processes of formulating a model and and to provide them with an introduction to relating fundamental principles to the the methods that are now available to mathematics and experimental outcomes for example, for developing word models quantitatively analyze biological data. were often more informative than the and methods for solving and analyzing Like many quantitative biologists, my solution itself. However, after marveling at systems of ODEs. From the perspective of a first exposure to mathematical modeling the awesome power of ODEs, we soon developmental biologist, a glaring omission was not in the context of cell biology or realized that the solution of some, or indeed from this book is any discussion of pattern developmental biology, but came through most sets of, ODEs was intractable, that formation or examples of diffusion-reaction examples from physical chemistry, there was no way to capture relevant details equations. Early work on partial differential physiology and population ecology. In these of complex biology with continuous equations and pattern formation by Alan fields, simple problems can be formulated variables, or that model predictions could Turing in the 1950s (Turing, 1952) and Hans using ordinary differential equations not be tested experimentally. As such, the Meinhardt in the 1970s (Gierer and (ODEs) with complete statements of the tool kit of ODEs used to learn the skills of Meinhardt, 1972; Meinhardt, 1977) provided state variables, such as initial conditions. As mathematical modeling is less useful for the stimulus for many theorists to enter the students, we learned to write ‘word-models’ developing the quantitative models that are field of developmental biology and attracted and to translate these into sets of ODEs. needed to describe problems in cell and quantitative biologists to challenge those Word models are narrative passages developmental biology. models. Given the lack of textbooks focused intended to translate the details of a Unlike physics or chemistry, biology has on mathematical models in developmental biological problem such that biologists and very few universal theories. In classical biology, students interested in modeling the mathematicians alike can understand the physics, theoretical frameworks can connect complex problems of modern cell and DEVELOPMENT 5270 BOOK REVIEWS Development 138 (24) developmental biology would be well biology. However, more advanced students there seems to be no other way to understand advised to augment this text with other books and quantitatively inclined developmental the mechanisms underlying developmental on modeling specific biophysical systems biologists will have to wait for textbooks that processes than to know, at the descriptive and with more targeted reading of extensive provide a more complete introduction to level, how an organism undergoes normal supplemental materials that accompany the computational tools that have seen extensive development. Chapter 2 focuses on primary literature of gene regulatory application in recent years. Drosophila development, appropriately networks, cell signaling and morphogenesis. because, as the authors point out, we have References Current state-of-the-art modeling efforts in more in-depth developmental knowledge Edelstein-Keshet, L. (2005). Mathematical Models developmental biology range from Bayesian in Biology (Classics in Applied Mathematics). New about the fly than about any other animal. York: Society for Industrial and Applied models to finite element models to agent- The treatment is systematic and clearly Mathematics. based models, but the model-building presented, with beautiful illustrations. Most Gierer, A. and Meinhardt, H. (1972). A theory of exercises and focus on ODEs presented in of the important concepts are presented here; biological pattern formation. Kybernetic 12, 30-39. Meinhardt, H. (1977). A model of pattern formation van den Berg’s text are still essential to form although, not surprisingly in a text of limited in insect embryogenesis. J. Cell Sci. 23, 117-139. an understanding of the field of mathematical size, much of the crucial evidence is not. It is Murray, J. D. (2007). Mathematical Biology: I. An modeling in biology. The tutorial forms a justifiable way to present material to the Introduction. New York: Springer. Segel, L. A. (1984). Modeling Dynamic Phenomena presented by van den Berg provide a concise student, presumably providing reinforcement in Molecular and Cellular Biology. New York: introduction to the principles of modeling for lecture material, but leaving the lecturer Cambridge University Press. and dynamical systems and are suitable for something of substance to talk about. Some Turing, A. M. (1952). The chemical basis of an introductory course in mathematical morphogenesis. Phil. Trans. Roy. Soc. B 237, 37-72. might argue that the descriptions of concepts don’t matter a whit, and what is more important is that the students can reason and can design or interpret experiments to establish for themselves how a concept is We hold these principles to established. The ideal probably lies in between. Perhaps in a book about principles, be self-evident the authors could have put more emphasis on some of the general principles of Richard Harland developmental biology experiments, such as the inferences that can be drawn from University of California-Berkeley, 163 Life Sciences gain- and loss-of-function experiments, Addition #3200, Berkeley, CA 9472, USA. approaches which enjoy so many variations. harland@berkeley.edu The boxes that include the methods are doi:10.1242/dev.069864 generally excellent, though they are not Principles of Development illustrated in later chapters with examples necessarily presented in a consistent manner: from real animals and plants. The principles The Cre-lox system in the mouse and By Lewis Wolpert and Cheryll Tickle and concepts could be re-stated more mutagenesis in the fish receive nice pink Oxford University Press (2011) 656 pages ISBN 978-0-19-954907-8 forcefully throughout the book, though, as boxes, but homologous recombination in £36.99 (paperback) they may be missed by the inattentive embryonic stem cells is in line with the text. reader. Along the way, boxes explain the The latter techniques are described in the What is to be taught in an undergraduate important experimental techniques that chapters on vertebrate development. An course on developmental biology? As in all provide approaches to questions. The introductory chapter to this section branches of biology, there is far too much figures are drawn in a consistent style, describes vertebrate development and known to be able to teach it all, and any which helps to give a coherent presentation common methods, and is followed by a introductory course would sacrifice depth. and lets the student focus on content. chapter on setting up the body axes. This Inevitably, choices must be made, and one Although the images are variants of the represents a change from the previous choice is to emphasize important principles kinds of drawings we have seen in original edition, in which these topics were covered and concepts of development across all journal articles and other textbooks, they are in a single chapter, and is one of the good organisms. Lewis Wolpert and Cheryll rendered here with style and clarity. The updates. The chapters on vertebrate Tickle, with a cast of impressive supporting photographs are usually well chosen, though development, just like the others, are clear authors, have made excellent selections in in some cases they don’t seem to be as clear and beautifully written and illustrated. Principles of Development. This is the or as relevant as they should be. For Chapters covering the more complex topics, fourth edition of the book and the thoughtful example, it isn’t clear why a well- such as somite and nervous system choice of topics that went into the first camouflaged California false hellebore, the development, follow as epigenesis edition is still evident, although there have source of the teratogen cyclopamine, is proceeds. At this juncture, the early also been many useful updates. shown, rather than the (admittedly grisly) embryology of other prominent model The book begins with some history and a cyclopic consequences of its action. animals, the nematode, sea urchin and summary of general concepts. The concepts Once the concepts are dealt with, the book ascidian, take center stage, and a chapter on are important ones, especially when framed goes justifiably into detail on different plant development rounds out the coverage by the title of the book, but they may be a organisms. It is difficult to grasp general of organisms. little dry out of the context of real concepts without knowing the descriptive The book then circles back to various organisms. However, one has to start background; although the plethora of terms developmental processes. Admirable somewhere, and the general concepts are and structures may be daunting to the student, examples from various phyla are used to DEVELOPMENT Development 138 (24) BOOK REVIEWS 5271 illustrate the process of morphogenesis, in figures that would clarify the molecular should be principles of development – after which underlying cellular processes can be mechanisms at play in threshold activation. all, evolution selects whatever process seen to give rise to changes in the shape of Later in the book, one might have expected happens to work and developmental biology the organism or tissue. The selection of a deeper treatment of hedgehog signaling is full of ad hoc solutions to problems. examples from diverse organisms is made and threshold responses, as that might be the Nevertheless, there are some core principles possible by the earlier descriptive coverage, clearest case of a morphogen gradient at that recur in development, suggesting that which no longer need get in the way of the work in vertebrates. And what these must be either ancient and inherited, or discussion of concepts. Germ cells and sex is the best evidence that these molecules arrived at by convergence. Anterior- determination are followed by gene really act as morphogens? It certainly isn’t posterior patterning by deployment of Hox expression, cell differentiation and simple, but many students can deal with genes might be an example of the former, plasticity, including another excellent the evidence. Similarly, an important whereas branching morphogenesis might be update in the current edition – inevitably, on developmental principle is that internal an example of the latter, for which it is stem cells and the plasticity of gene organs achieve a high surface area by arguable that each organ might employ a expression. branching morphogenesis. The treatment different morphogenetic program. is again a bit glib; genes and proteins It is inevitable that a reviewer will raise that promote or inhibit branching are some criticisms; nevertheless, as it stands Lewis Wolpert and Cheryll enumerated, but I don’t think the authors this is an outstanding text with a well- can have stood up in front of a class and digested and comprehensive presentation of Tickle ... have made tried to argue that this really explains current views in developmental biology. It is excellent selections in branching, unless their students are more a text I can enthusiastically recommend for passive than ours. One hopes that the adoption in developmental biology courses. Principles of Development undergraduates will test the lecturer’s For those courses that have previously A book by Wolpert and Tickle would be understanding at points like this and demand used this text, is the fourth edition worth the incomplete without extended treatment of a deeper explanation, or an admission that upgrade? The hardback edition is expensive the limb, and a chapter on organogenesis the emperor indeed has no clothes. and it would be hard to justify the burden of includes vertebrate and insect limbs, eyes Finally, although the opening chapter an expensive new edition on a fresh set of and various internal organs. The authors’ addresses what may be some important undergraduates when the cheaper previous expertise in limb development is reflected principles and concepts, these should be editions of Principles of Development might in the greater citation of experiments in this more explicitly re-stated throughout the be available. The paperback is a better deal area, though this may challenge the book. I don’t think that students find these and my review copy hasn’t fallen apart yet. undergraduate who wants a clear-cut story. concepts obvious, particularly when the Still, as Oliver Wendell Holmes said, “A One has to admire Wolpert for giving details, terms and descriptions come thick man is usually more careful of his money prominent treatment to his progress zone and fast. Indeed, one might ask why there than of his principles.” model, which most people might present as a great idea that is no longer tenable. But, perhaps if a book is to emphasize principles, it only matters if they are good Fast-forward: the fourth possibilities, not whether they are currently supported. dimension in development The book closes with an excellent summary of developmental neurobiology, a Elaine Dzierzak* and Catherine Robin chapter on post-embryonic growth and development, an expanded treatment of Erasmus MC, Erasmus Stem Cell Institute, Dept of Cell regeneration and a good evo-devo summary. Biology, P.O. Box 2040, 3000 CA Rotterdam, The If the book is to remain manageable in Netherlands. size, it is inevitable that some favorite topics *e.dzierzak@erasmusmc.nl of the reader might be glossed over. doi:10.1242/dev.066969 However, despite the admirable emphasis on principles and concepts, I occasionally Imaging in Developmental Biology: embryo, from the zygote to gastrulation, to felt short-changed. With these authors, I A Laboratory Manual organogenesis, and birth, has been a subject might have expected a deeper treatment of of fascination and science (fiction?) for Edited by James Sharp and Rachel O. Wong what surely must be one of the most centuries. This fascination is reflected in the Series Editor, Rafael Yuste important principles: the existence of many historical drawings of developing Cold Spring Harbor Laboratory Press (2011) 883 Pages threshold responses to morphogens – embryos and by advances in the field of ISBN 978-0-879699-40-6 (paperback), 978-0- molecules that diffuse from a source and set embryology that came with the invention of 879699-39-0 (hardback) $165 (paperback), $246 (hardback) up a graded concentration. Instead, when it the microscope. With the aid of microscopy, gets to the nitty gritty of boundaries, the the field advanced from drawings of activating and repressing activities of one Development is a bit like Star Trek, the embryos to static images of fixed sections, gradient (such as hunchback or dorsal) are long-running television series in which which could be rendered, with some mental mentioned, but how one protein both ‘space’ is the final frontier. For effort, into three-dimensional (3D) activates and represses is not explained. development, the final frontier is the fourth structures. However, comparisons of Indeed, the text gets pretty dense and lacks dimension, ‘time’. Time travel through the embryos at different formative stages could DEVELOPMENT 5272 BOOK REVIEWS Development 138 (24) only hint at the patterns of dynamic cell provided on embryo accessibility and size, groups of cells. The excellent figures and growth and morphological change that tissue transparency, different cell-marking descriptions that detail how to culture occur during development, which recent techniques, phototoxicity, mounting embryos, hold them in place and manipulate molecular and genetic analyses have begun methods and compatibility with imaging them will be of great use for studying cell- to uncover. Importantly, the current resolution, and image analysis. Chapters fate determination and migration in early advances being made in innovative, real- are written by experts in the field, and each mouse development. Chapters 19 and 23 time imaging technologies and in the starts with a brief introduction into the describe the imaging of embryo slice computational processing of images have mechanisms of development being cultures in various species and tissues. As an now fast-forwarded the field boldly into the addressed and with a description of the important aspect of neural development, the dynamic fourth dimension. These advances specific imaging method used, followed imaging of circuit formation is the focus of are now summarized and explained in a by one or more protocols. Concise Chapters 24-35, which are aimed at newly published book on imaging, Imaging troubleshooting, discussion, recipes, web specialists studying neuron excitation, in Developmental Biology, edited by James resources and reference sections provided axon pathfinding or synapse formation. Sharp and Rachel O. Wong, both experts in at the end of each chapter are of added However, these approaches are also of this field. benefit in ensuring the success of the broader relevance to research in other approach. developmental systems. Live imaging of cells is the focus of Imaging multicellular tissues and organs It is a valuable guide ... Section 2. Cell-labeling protocols in as a whole dynamic entity is covered in Chapters 8-13 provide an extensive Section 3. The first two chapters (Chapters 36 although serious training coverage of dye injection and and 37) explain how to quantify morphogen might be required to electroporation techniques for groups of, gradients over time in Drosophila embryos. and for single, cells in chick, mouse, We found these chapters harder to understand perform the more Xenopus and zebrafish embryos. The and aimed more at the specialist reader. By complex experiments protocols provide important technical contrast, Chapters 38-43 on cell movement details about, for example, injection pipette describe more commonly used methods to Imaging in Developmental Biology is an production, electrode placement, voltage acquire high-resolution dynamic movies of excellent resource from which both novices strength, pulse duration and intervals. Other cells or subcellular proteins during and experienced researchers can obtain labeling techniques covered include the morphogenesis in Xenopus, zebrafish, chick, current state-of-the-art embryo-imaging difficult MARCM (mosaic analysis with quail and mouse embryos. Protocols protocols for studying key developmental repressible cell marker) in Drosophila and provided in this section include how to events, such as cell-fate determination, MADM (mosaic analysis with double generate Xenopus and zebrafish embryos morphogen gradient formation, cell-cell marker) in mice. Commonly used direct with mosaic fluorescent reporter expression interactions, cell migration and transgenesis and knock-in strategies with and how to prepare and mount tissue explants morphogenesis. The eye-catching cover fluorescent marker genes, as well as Cre- or whole embryos for long-term imaging, immediately attracted passing lab members, Lox recombination and fluorescence- together with useful troubleshooting tips. encouraging them to browse the book, photoactivation methods, are presented in This section also contains a well-illustrated which they did with increasing interest. the context of specific developmental protocol to perform high-resolution The first comment often expressed was: questions concerning cell-lineage tracing. multiphoton time-lapse imaging of a “I did not know that we could do so much!” The relative merits of the different strategies developing chick embryo and protocols Upon first perusal, this comprehensive are clearly described in Chapter 13. for 3D time-lapse imaging of epithelial book seems almost overwhelming with Chapters 14-23 cover live cell imaging of morphogenesis and of the mouse an impressive 57 chapters and seven cell migration, mostly of the neuronal metanephric kidney. Two relatively new appendices. But it does contain just about system. Particularly useful here are the imaging technologies are presented in everything known about imaging embryos. descriptions of the use of the Chapters 44-46 that allow live imaging of This is not surprising as the volume is based, photoconvertible fluorescence marker developing whole embryonic organs – in part, on the popular and excellent Cold Kaede to study neuron birth dating in optical coherence tomography (OCT, an Spring Harbor imaging course. The editors zebrafish embryos, and the explanation of optical version of ultrasound used to have organized the book into four large DNA injection methods, embryo image high-speed events) and a non-invasive sections, which contain chapters that embedding, image acquisition and software ultrasound technology used to image are frequently and conveniently cross- usage in the context of studies of zebrafish 3D organ geometry (which allows referenced. A particularly helpful table is retina and lateral line development. As developmental events to be imaged over provided in Chapter 1 that guides the reader mouse developmental biologists, we found time). to specific protocols of interest in different the zebrafish protocols and figures (in After single cells and organs, Section 4 animal models. Chapters 16-18) easy to understand. Of focuses on imaging the whole embryo in 3D Section 1 (Chapters 1-7) provides a special interest to us were Chapters 20 and and 4D. These chapters provide detailed general entry into the imaging of common 21, as the details of pre- and post- protocols for the collection of spatial and model organisms. This section’s emphasis gastrulation mouse embryo dissections with temporal patterns of gene expression, for on the advantages and disadvantages of excellent accompanying figures are an embryo phenotyping and for generating each model organism allows researchers to important resource for our students. These static or dynamic 3D atlases of model evaluate quickly which animal model and chapters contain detailed protocols for systems. Of particular interest is Chapter 48, procedures might be most useful for their tagging cells with dyes, grafting cells into which provides a didactic description of specific investigations. Information is embryos and for electroporating DNA into the intellectual and technical efforts of DEVELOPMENT Development 138 (24) BOOK REVIEWS 5273 the Berkeley Drosophila transcription particular interest to developmental ways in which gene expression is regulated network project, which has produced biologists. post-transcriptionally, have meant that the a computationally analyzable, gene Altogether, Imaging in Developmental field of RNA has undergone rapid growth in expression and morphological 3D atlas Biology is a book for those Development the past few decades. This rapid growth has of a blastoderm embryo. The use of readers who are curious to know more recently increased even further because of hardware and software is also well about new technical developments and the discovery of RNA interference (RNAi), explained and illustrated in detail, including possibilities within the exciting field of as well as the discovery that small RNAs, chapters on optical projection tomography imaging. It is a valuable guide and a very distinct from tRNA and snRNA, undergo (OPT), X-ray micro-computed tomography helpful laboratory manual for students, processing to fulfil a range of cellular (mCT), episcopic fluorescence image although serious training might be required functions. These include the regulation of capturing (EFIC), high-resolution episcopic to perform the more complex experiments. transposable element transposition by microscopy (HREM) and macroscopic Seven appendices at the end of the book are piRNAs, regulation of translation by magnetic resonance imaging (mMRI), with particularly helpful for new people entering microRNAs and still poorly explored large detailed information again provided for the field and include a must-have list of non-coding RNAs (ncRNA). Many of these troubleshooting as well as additional web fluorescent filters and excitation/emission ncRNAs have turned out to have important resources. Descriptions of the advantages, spectra, lens cleaning tips, a list of cautions roles in development and during disease disadvantages, limitations and future and potential disasters, and an all-important processes, such as cancer. Therefore, it is prospects of each technique will definitely glossary of terms. The book is pleasant to clear that all aspects of RNA molecular assist readers in choosing the appropriate read, with its clever use of illustrations, biology have now become central to our method for their own application. The photos and online protocol videos. Thus, understanding of cell and developmental fourth dimension, time, is finally reached in we highly recommend this book and biology. the last chapters (56 and 57). Protocols are hope that multidisciplinary collaborative Despite the rapid growth and exciting provided here for high-volume 3D time- expertise in biology, imaging, image discoveries made recently in the field of lapse imaging of live adult Caenorhabditis analysis, computer science, visualization RNA, to my knowledge there has not elegans and of zebrafish and Drosophila and database construction will continue to been a comprehensive textbook for embryos. Digital representations of these fast-forward 4D imaging techniques and, undergraduates and postgraduate students embryos permit cell tracking in time, consequently, our knowledge of that focuses on the molecular biology of revealing their origin and fate, which is of development. the cell from the perspective of RNA. Molecular Biology of RNA, by David Elliot and Michael Ladomery, now plugs this gap. This comprehensive textbook is pitched at just the right level and explains A molecular view of the life the concepts in sufficient detail to make them come to life without swamping the and time of RNA uninitiated with confusing information and jargon. The authors have to be Ilan Davis congratulated on the comprehensive nature of the textbook, which means that even Department of Biochemistry, The University of Oxford, RNA aficionados will find useful South Parks Road, Oxford OX1 3QU, UK. information within its pages. At the same ilan.davis@bioch.ox.ac.uk time, it is a relatively short tome (400 or so doi:10.1242/dev.067033 pages) and reasonably priced. Molecular Biology of RNA now regarded to have credible catalytic After introducing some important properties through the availability of its 2- general principles of RNA structure, By David Elliot and Michael Ladomery OH, a reactive group that replaces a non- catalysis and RNA-binding proteins, the Oxford University Press (2010) 460 pages ISBN 978-0-19-928837-3 reactive ‘O’ atom in DNA. Moreover, its chapters of the book are structured £34.99/$55 (paperback) catalytic roles include key functions in the according to the life cycle of an mRNA, most important molecular machines of the starting with its birth in the nucleus, its Following the discovery of the structure of cell, such as the spliceosome and ribosome. splicing and processing and exit from the DNA and during the early days of molecular In hindsight, it would perhaps not be so nucleus, and moving onto its subsequent biology, RNA was considered to be a less surprising if the RNA world hypothesis cytoplasmic localisation, translation and interesting cellular component to study than turned out to be correct. This hypothesis degradation. These broad themes are DNA. This was primarily because RNA states that the first life forms on our planet broken down into more detailed concepts; was thought to be simply a molecular were RNA-based simple cells in the pre- for example, RNA processing is covered photocopy of the genetic blue print stored biotic soup. RNA is certainly a better by chapters on co-transcriptional in DNA. But how things have changed! candidate than either DNA or proteins for a processing, splicing, alternative splicing, Since those early days, our understanding of self-replicating molecule that acts both as a and splicing defects in development and the cellular roles of RNA has changed template for, and that has the necessary disease. Nuclear exit is broken down radically. RNA is now considered to be of catalytic machinery to perform, its own into the processes of mRNA central importance to both molecular replication. Moreover, the discovery that nucleocytoplasmic trafficking and ncRNA biology and cellular function. Far from only most mRNAs are spliced, and the gradual nucleocytoplasmic trafficking. It is clear containing genetic information, RNA is uncovering of a breathtaking number of that the authors have placed greater DEVELOPMENT 5274 BOOK REVIEWS Development 138 (24) emphasis on nuclear events than on those Although Molecular Biology of RNA cytoplasm, such as mRNA localisation, in the cytoplasm. Although this makes the offers a good systematic introduction to RNA translation and degradation. I am already textbook a little unbalanced, it does mean research, it is also important to consider the looking forward to the next edition, in which that for anyone interested in nuclear events limitations of the book. The diagrams are these deficiencies can be addressed, perhaps related to RNA, there is considerable perhaps a little too simplistic and would at the expense of making the textbook a little detail. By contrast, for topics like mRNA certainly have benefited from a more stylised longer and increasing its cost slightly. localisation, the book offers a simplified approach and perhaps from being in colour. References overview to less experienced scientists, However, this may have pushed up the cost Atkins, J. F., Gesteland, R. F. and Cech, T. R. but lacks necessary details. of the textbook. As mentioned earlier, (2010). RNA Worlds: From Life’s Origins to Diversity in Gene Regulation. New York: Cold Spring Harbor perhaps most importantly, there is an over- Laboratory Press. representation of events in the nucleus, This comprehensive Darnell, J. E. (2011). RNA: Life’s Indispensable particularly splicing, at the expense of Molecule. New York: Cold Spring Harbor textbook is pitched at just equivalent levels of detail on topics in the Laboratory Press. the right level and explains the concepts in sufficient detail to make Epigenetics in all its glory them come to life 1,2 Mellissa R. W. Mann The book is well written, easy to follow Department of Obstetrics & Gynaecology and and, on the whole, strikes a good balance Department of Biochemistry, Schulich School of Medicine between providing sufficient detail and and Dentistry, University of Western Ontario, London, providing a simplified description of Ontario, Canada N6A 5W9. Children’s Health Research complex concepts. The authors have Institute, London, Ontario, Canada N6C 2V5. succeeded in producing a volume that is mmann22@uwo.ca very useful for both undergraduate and doi:10.1242/dev.069989 graduate students starting a research career in an RNA-related topic, as it includes a Epigenetics methylation, histone modifications, changes comprehensive glossary at the end of the Linking Genotype and Phenotype in in chromatin structure, and effects of non- book. The textbook will still be of value Development and Evolution coding RNAs. This book includes five to more experienced researchers from chapters on molecular epigenetics, covering Edited by Benedikt Hallgrímsson and Brian K. Hall other fields that wish to get a quick various organisms and topics from asexual comprehensive introduction to RNA University of California Press (2011) 472 pages organisms in the study of epigenetic ISBN 978-0520267091 (hardback), 978-0520948822 research or to get started with a particular variation to epigenetics and human disease. (eBook) subtopic, such as splicing or mRNA One chapter highlights neural development £59/$68 (hardback), $85 (eBook) localisation, as each section has a well in which cell-fate switches are intimately chosen set of references as an entry point Ask ten scientists their definition of linked with epigenetic changes. For to a field. When deciding whether to epigenetics and you may get ten answers. In example, transition from a neural stem cell purchase the book, readers may wish to its simplest form, epigenetics can be defined to a progenitor cell involves a switch in co- consider what else is available covering as above (epi) the level of genes (genetics), factor associations. In response to Notch the topic of RNA. There are a number of and in the book entitled Epigenetics: effector molecules, the HES1 repressor other excellent textbooks that focus on Linking Genotype and Phenotype in complex is transformed into a HES1 methods used in the RNA field; for Development and Evolution, the editors, activator complex, thereby inducing a example, RNA Worlds: From Life’s Benedikt Hallgrímsson and Brian K. Hall, progenitor cell fate. A different mechanism Origins to Diversity in Gene Regulation. have assembled 23 chapters that collectively may be utilized in neuronal fate In general, these textbooks are more embody epigenetics as described by this specification in the neocortex. Changes in specialised, more expensive and appeal to broad definition. Although the book is DNA looping and nuclear matrix binding more experienced researchers. This year organized into four parts, it can be distilled may specify an upper layer neocortical fate. has also seen the publication of RNA: into three themes that each discusses a This chapter describes the current Life’s Indispensable Molecule by James more detailed interpretation of the field: understanding of various epigenetic Darnell, which, like the textbook by Elliot molecular epigenetics, classical epigenetics/ mechanisms involved in neural cell fate and Ladomery, is also being sold at an epigenetic interactions, and epigenetic decisions. affordable price and is also meant for interactions and evolution. The second theme of the book is young researchers at the beginning of their In its modern molecular reiteration, classical epigenetics or epigenetic research careers. However, Darnell uses a epigenetics is defined as a change in gene interactions. It is referred to as classical very personal and subjective style to activity without a change in DNA sequence. because the term ‘epigenetics’ was first describe the history of RNA research – a Most molecular definitions of epigenetics coined by Conrad Waddington in 1942. very different approach from the also include the idea of heritability, or Waddington’s definition of epigenetics was systematic textbook description employed memory of gene activity, through cell ‘the branch of biology which studies the by Elliot and Ladomery in Molecular division. Here, epigenetic modifications causal interactions between genes and their Biology of RNA. modulate gene expression through DNA products which bring the phenotype into DEVELOPMENT Development 138 (24) BOOK REVIEWS 5275 being’ (Waddington, 1942). In Chapter 7, have evolved long snouts with upturned these definitions of epigenetics is the Ellen Larsen and Joel Atallah introduce mouths suitable for planktonic prey, have complex and finely tuned choreography of epigenesis as the gradual unfolding of lost group cannibalistic behaviour and development. In the not too distant future, structure and function during development display conspicuous courtship displays. In we will probably find that these definitions and present the analogy of a fertilized hen’s shallow, nutrient-rich lakes, threespine are intimately linked. As stated by Root egg that develops into a downy chick: sticklebacks have short snouts and wide Gorelick, Manfred Laubichler and Rachel scrambling the egg retains all the genetic mouths for feeding on benthic invertebrates, Massicotte in Chapter 6 ‘the molecular material and yet there is no development. display group cannibalistic foraging and epigenetic signals [can be considered] the This exemplifies the point of epigenetic have inconspicuous courtship, consisting nuts and bolts underlying the classical interactions that occur above the gene of dorsal pricking. This chapter explores epigenesis sensu Waddington’. level. Here, epigenetic interaction is the the phenotypic plasticity of an ancestral This book celebrates epigenetics in all umbrella term for cell migration, physical population in response to novel its glory. As a first of its kind, I recommend interaction among cells and tissues, environments and its role in influencing this book to researchers and graduate mechanical forces, embryonic induction subsequent evolutionary change. students who want to widen their (including cell signalling and hormones), In all languages, including the language perspective of epigenetics and its role in and interactions between cells and their of biology, words and terms can evolve and, development and evolution. Because of the intrinsic or extrinsic environment. All thus, their meaning can change. Over time, division in meaning, this book does require these interactions may play a role in the modern molecular definition of the reader to switch gear depending on generating the ‘epigenetic landscape’ ‘epigenetics’ has supplanted other whether the chapter is on molecular or through which a cell must transverse to definitions. In Epigenetics: Linking classical epigenetics. Furthermore, it is reach its final differentiated state within Genotype and Phenotype in Development steeped in epigenetic, development and a tissue or organ. These epigenetic and Evolution, Hallgrímsson and Hall evolution terminology. This makes it less interactions are discussed in nine chapters, provide a comprehensive selection of than suitable for the undergraduate student. each of which focuses on the development epigenetics in its many forms and appeal to However, this book would be an excellent of a specific cell type, tissue or organ. One the reader to accept a broader definition of resource for a graduate course in classical chapter describes the mechanical force of epigenetics – one that includes all things epigenetics, or epigenetic interactions and muscle activity on bone as an epigenetic epigenetic: not just molecular epigenetics, evolution. stimulus for developmental change. Using but also classical epigenetics and epigenetic Reference the mammalian jaw as the model system, interactions related to evolution. Waddington, C. H. (1942). The epigenotype. the effects of mechanical force (muscle Importantly, the context inherently linked in Endeavour 1, 18-20. force, bite force and compression load) on lower mandible condylar cartilage growth are explored. Evidence is presented for increasing force leading to shorter, wider A wake-up call to delve condylar cartilage growth and decreasing force for longer, thinner condylar cartilage deeper into the cell growth. This chapter illustrates mechanical forces on development as an epigenetic Wendy A. Bickmore mechanism. MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh, Ask ten scientists their Edinburgh EH4 2XU, UK. definition of epigenetics W.Bickmore@hgu.mrc.ac.uk doi:10.1242/dev.067025 and you may get ten answers The Nucleus – transcription, replication, repair – occur. In developmental biology papers it is not Edited by Tom Misteli and David L. Spector The third theme, covered by six chapters uncommon to find a final summary figure in Cold Spring Harbor Laboratory Press (2011) 517 pages in this book, is epigenetic interactions as a ISBN 978-0-879698-94-2 which a signaling pathway ends up pointing $135 (hardback) framework for evolution. For example, one into an oval-shaped nucleus, devoid of any chapter focuses on the epigenetic integration structure or organization, save for a linear of various head modules (brain, Why should a developmental biologist be depiction of a target gene locus. However, the bone/cartilage, muscle, eyes, tongue, teeth, interested in a book about the nucleus? nucleus is not a homogenous space and muscles, sinuses/cavities) in development Almost 80 years ago, Conrad Waddington neither is the genome in its natural nuclear and its variations during human craniofacial put forward ideas about how gene products environment arranged in a linear fashion. evolution. Another chapter discusses the could regulate development. In modern The contributions in this book, from concept of adaptive plasticity and genetic parlance, much of development is the result international leaders in the field of nuclear assimilation in evolutionary change, as of the differential use of the same genome in organization and function, are based exemplified by the phenotypic and different cell types and at different upon the premise that we cannot really behavioural changes in threespine developmental stages within the same understand how genomes function without an sticklebacks in different ecotypes. In deep, organism. This originates in the nucleus, appreciation and understanding of their nutrient-poor lakes, threespine sticklebacks where the processes that act upon the genome natural cellular environment – the nucleus. DEVELOPMENT 5276 BOOK REVIEWS Development 138 (24) The 28 chapters are organized to provide There are several examples of proteins that They describe the amazing nuclear a comprehensive overview of nuclear are expressed within a particular cell reorganization of the genome that occurs, compartments and their components (e.g. type, but are sequestered into a nuclear after birth, in the rod cells of nocturnal nuclear membrane, nuclear pore complex, compartment that renders them functionally mammals and they emphasize how such a chromosome territories, Cajal body, inactive. Thoru Pederson gives a fascinating fundamental aspect of nuclear organization nucleolus), to discuss how this organization example of this (sequestration of the Hand1 can be turned on its head in the face of relates to function (transcription, DNA transcription factor into the nucleolus of selection pressure – in this case, to facilitate replication and repair, RNA processing) trophoblasts) in his chapter on the nucleolus. the passage of photons to photoreceptors in and to describe the defects in nuclear This should be a wake-up call for low light levels. organization in human disease. The focus is developmental biologists to delve deeper There are other equally fascinating primarily on the nucleus in mammalian into subcellular organization. Conversely, examples to be found in this book where cells, but there are also discussions on other most cell biology of the nucleus is still nuclear organization impinges directly simpler model organisms – budding yeast, studied in cell lines rather than in real on developmental processes. Nuclear Caenorhabditis elegans and Drosophila. biological organisms or embryos. There is condensation in terminally differentiated Each chapter is relatively short and clearly scope to bridge these two disciplines. cells and aberrant nuclear organization in accessible, making this a great resource to Indeed, in their chapter on Chromosome cancer are just two examples that come dip into. Illustrations are used sparingly but Territories, Thomas and Marion Cremer immediately to mind. So, although not are well chosen. provide a superb example of the benefits targeted at developmental biologists, if your The main target audience for this book that can come from considering nuclear interest in the nucleus is piqued, then this is likely to be teachers and students of organization in a developmental setting. book is a good place to start. cell biology. The most interest for developmental biologists will lie in those chapters that deal with the organization of the genome and the transcriptional A practical guide to human machinery within the nucleus. Spatial and temporal changes in genome organization stem cell biology are increasingly recognized as important aspects of gene regulation, especially in Neil Singh and Ludovic Vallier* stem cells and differentiation. Thus, from a developmental biologist’s perspective, it is The Anne McLaren Laboratory for Regenerative disappointing that no specific chapter is Medicine, Department of Surgery, University of dedicated to the nucleus in development, but Cambridge, Cambridge CB2 0SZ, UK. there are nuggets of relevant information *lv225@cam.ac.uk within most chapters. The chapter on dosage doi:10.1242/dev.067256 compensation (written by Jennifer Chow and Edith Heard) is of direct relevance to Human Stem Cell Technology and manageable and appropriate for a newcomer events that occur in early embryogenesis, Biology: A Research Guide and to the field or for an early career scientist and a chapter on Lamin-binding proteins Laboratory Manual working with human pluripotent cell lines for (written by Katherine Wilson and Roland the first time. Edited by Gary S. Stein, Maria Borowski, Mai X. Luong, Meng-Jiao Shi, Kelly P. Smith Foisner) emphasizes the fact that proteins of The editors are all based at the Center for and Priscilla Vasquez the nuclear periphery that link the nucleus to Stem Cell Biology & Regenerative Wiley-Blackwell (2011) 419 pages the cytoskeleton are particularly important Medicine at the University of Massachusetts ISBN 978-0-470-59545-9 in regulating the position of the nucleus in Medical School. The individual chapters are £93.50/€112.20 (hardback) specific cell-types or tissues (e.g. retina and written predominantly by scientists from neurons) and in relaying signals from the Do we need another book on human stem cell institutes on the East coast of the United cytoplasm to the nucleus. biology? The field is fairly long in the tooth States, although some contributors are based now, thirteen years after Thomson first in Australia, Canada and China. The book is derived human embryonic stem (ES) cells divided broadly into five sections: an No specific chapter is (Thomson et al., 1998). There are many introduction; two sections on the culture and dedicated to the nucleus books that cover the theoretical aspects of the characterisation of human pluripotent stem discipline (Oderico et al., 2004) and others cells; and two sections covering more recent in development, but there that attempt to collate protocols useful to technologies and applications relevant to are nuggets of relevant human stem cell biologists (Sullivan et al., human ES cells. 2007). Nevertheless, the new book Human In the introduction, the authors have information within most Stem Cell Technology and Biology succeeds managed to distil over 50 years of stem cell in combining both of these characteristics, advances in just a few pages of text. chapters providing not only a clear account of the Although this may be too short for Developmental biologists often ask scientific discoveries underpinning human experienced scientists hoping for a colourful where and when a gene or protein is stem cell biology, but also a useful range of narrative history of each breakthrough, we expressed in the developing organism. laboratory protocols. The end product may be think it does well to bring even novice However, rarely do they ask precisely where less comprehensive than Lanza’s classic text readers up to speed with current thinking in within the cell a particular protein is located. (Lanza et al., 2009), but it is perhaps more stem cell biology, from the bottom up. DEVELOPMENT Development 138 (24) BOOK REVIEWS 5277 References The sections containing protocols are (using stem cells or insights into growth Lanza, R., Gearhart, J., Hogan, B., Melton, D., excellent and provide the perfect conditions to help repopulate and regenerate Pedersen, R. A., Thomas, E. D., Thomson, J. A. framework for experimental work on degenerative and diseased organs). and Wilmut, I. (2009). Essentials of Stem Cell human stem cells. Each chapter is devoted Although brief, the final chapter manages to Biology. Maryland Heights: Academic Press. Odorico, J., Pedersen, R. A. and Zhang, S. (2004). to a separate technique and begins with an encapsulate the major recent breakthroughs Human Embryonic Stem Cells. Abingdon: Taylor & extremely helpful overview that underlines and future prospects for cell replacement Francis. the basic steps, and importance, of each therapies in ectodermal, mesodermal and Sullivan, S., Cowan, C. A. and Eggan, K. (2007). Human Embryonic Stem Cells: The Practical protocol. The layout has been well thought endodermal tissues. Handbook. Hoboken: Wiley-Blackwell. out, supplementing the customary One of the book’s major strengths is Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., ‘equipment’ and ‘procedure’ sections with the accompanying DVD. It provides Ichisaka, T., Tomoda, K. and Yamanaka, S. helpful tables, log sheets with blanks to be printable copies of the protocols from the (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell filled in and space for the reader to make book, and even has a helpful search tool, 131, 861-872. their own notes in the margin. These which we found extremely useful. The Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., protocols have been used as part of DVD also contains six videos, which Waknitz, M. A., Swiergiel, J. J., Marshall, V. S. and Jones, J. M. (1998). Embryonic stem cell lines practical courses in stem cell biology at the demonstrate good laboratory practice, derived from human blastocysts. Science 282, University of Massachusetts Medical aseptic technique and how to harvest, 1145-1147. School for several years, and this is evident passage and thaw cells. We would strongly by the careful explanation of each recommend that laboratories use these technique in the book and the thoughtful videos as part of the induction of new addition of pros and cons of each members to stem cell labs, as few laboratory Other recent books of interest technique. members have the time or training to offer Haldane, Mayr, and Beanbag Genetics By Krishna Dronamraju Later sections of the book will appeal to such a clear and standardised tutelage on the Oxford University Press (2011) 296 pages established stem cell investigators as they basics of laboratory practice and stem $34.95 (hardback) summarise the latest in bioinformatic, cell culture. The lead editor, Professor MicroRNAs in Development: Methods and genomic, epigenetic and proteomic Gary Stein, provides much of the training Protocols analyses of human stem cells. These in these videos himself. The book also Edited by Tamas Dalmay Springer (2011) 227 pages chapters provide a brief account of the boasts a student companion website £85.50 (hardback) logic and application of these various (http://www.wiley.com/go/stein/human) Developmental Biology, 9th edition techniques, and feature tables and pictorial which is supposed to collate updates, By Scott Gilbert representations of the scientific basis of the amendments and additional resources. Sinauer (2010) 711 pages techniques. This is most notable in the However, we were disappointed to discover $129.95 (hardback) chapter on epigenetics. that at the time of writing there were no Plant Transformation Technologies Edited by C. Neal Stewart, Jr, Alisher Touarev, Four years after Yamanaka’s group first additional resources available. Vitaly Citovsky and Tzvi Tzfira successfully reprogrammed differentiated Wiley-Blackwell (2011) 296 pages adult human dermal fibroblasts into £140 (hardback) To the beginner, the field pluripotent cells (Takahashi et al., 2007), The Dynamic Genome: A Darwinian much attention should be paid to the of stem cell biology ... can Approach By Antonio Fontdevila chapter devoted to reprogramming and Oxford University Press (2011) 232 pages seem impossible to induced pluripotent stem cells. It outlines £49.95 (hardback) the differences between reprogramming navigate. This book will RNA: Life’s Indispensable Molecule during fertilisation and during somatic cell By James E. Darnell act as an excellent guide. Cold Spring Harbor Laboratory Press (2011) 416 pages nuclear transfer. The chapter describes the $40 (hardback) major developments in reprogramming, Mechanisms of Life History Evolution such as the use both of cell extracts and of We would recommend this readable and Edited by Thomas Flatt and Andreas Heyland transcription factors, most notably the well-organised book to all laboratories Oxford University Press (2011) 504 pages Yamanaka factors: Oct4, Sox2, c-myc and dealing with human ES cells. We envisage £45 (paperback) Klf4. The chapter does well to highlight that a laboratory copy will prove to be Epigenetics: The Ultimate Mystery of the limitations of the current protocols, as invaluable as a reference text for all new Inheritance By Richard C. Francis well as recent attempts to improve the members of your laboratory, and the later W. W. Norton & Company (2011) 234 pages efficiency and safety of classical directed sections will be of benefit to more senior £19.99 (hardback) reprogramming using the Yamanaka investigators. Although not the most factors. energetic nor the most exhaustive book of Much has been made of the potential this type on the market, this volume applications of human stem cell biology. succeeds by summarising the historic and The final section deals with these recent research breakthroughs in human ES applications. These include the use of stem cell science and combining this with cells in drug screening (testing various types excellent and reliable laboratory protocols. and doses of medications to streamline To the beginner, the field of stem cell the drug development process); stem cells biology – with a burgeoning number of as in vitro models of disease (to principles, terms and techniques to master – further understanding of aetiology and can seem impossible to navigate. This book pathogenesis); and stem cells in cell therapy will act as an excellent guide. DEVELOPMENT

Journal

DevelopmentThe Company of Biologists

Published: Dec 15, 2011

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