13
5555 The embryo is a remarkable self- assembly machine. From a single cell, the fertilized egg, arises all of the differentiated cell types of the body. Embryos unfold in an elegantly choreographed manner that we strive to understand by observing the process, dissecting it into smaller bits, and mucking up the works by expressing too much or too little of some protein. Yet the mystery remains and, as knowledge and technology advance, we understand more about the depth of its complexity than about the process itself. Given the beauty and intricacy of the developing embryo, it is a lofty challenge to put the current state of information in a form that is both understandable and captures the imagination of students of biology at the undergraduate and graduate level. Scott Gilbert has met this dual challenge in the latest edition of Developmental Biology. He has caught the excitement of the field in a remarkably lucid way. The book starts by building from first principles and defining concepts, and then moves toward the details of morphogenetic processes themselves and what is known about their molecular bases. This book is worth investing in because it has been nicely expanded and updated over the previous versions, and also has much improved graphics. Although developmental biology has historically deep roots, some of the seminal work of the past is often ignored. Gilbert is keenly aware of this and does a wonderful job of putting the study of developmental biology in historical context. He describes the importance of development for understanding evolution, and discusses how it influenced Darwin’s discovery of the origin of the species. He frequently refers to the work of individuals who pioneered different aspects of experimental embryology and made pivotal discoveries that still influence thinking today. He also discusses the interesting interface between embryology and genetics, two fields that once were thought of as different disciplines, but that clearly have become integral to one another and are nearly indistinguishable today. The book does a very nice job of looking at the developing embryo at many levels, from the submicroscopic to the macroscopic. Given the importance of regulatory and coding regions of the genome, and the proteins that they encode, Gilbert provides an excellent introduction into the fundamentals of differential gene expression. He explains basic concepts in cell biology and genetics, particularly those that are integral for developmental biology, such as cell interactions and cell signaling. Furthermore, there is a broad introduction to many different organisms so that the book does not seem too ‘vertebrate-centric’. Of course, there is more detail and attention given to the better characterized ‘model’ organisms, but not at the expense of keeping a broad perspective. Sprinkled throughout the text are excellent illustrations that help the reader visualize the processes under study. The book is organized into four large sections, each of which is subdivided into chapters. The first section presents the background information that is essential to understanding the concepts of biology, both historically and scientifically. The second section discusses early events in development, starting with fertilization and proceeding to axis formation. The third section deals with particular types of tissues, ranging from the formation of the nervous system to the limb. Finally, the book ends with a discussion of the medical implications of developmental biology and how development can instruct our understanding of evolution and vice versa. This section also includes a nice chapter, contributed by Susan Singer, that provides an overview of plant development. For those whose primary interest is plant developmental biology, this section may seem to provide too little coverage of this topic and to come too late in the book. It is safe to say that the book is mostly one on animal developmental biology. In conclusion, I highly recommend Gilbert’s Developmental Biology to students at both the university and post- graduate level. For that matter, it’s a very good read for more advanced investigators as well, and is a good resource for checking up on the latest research in an area that is outside of your own. It is up-to-date and is written in an engaging style that captures the excitement of developmental biology today. From egg to organism Marianne Bronner-Fraser California Institute of Technology, Pasadena, CA, USA e-mail: [email protected] Development 130, 5555 © 2003 The Company of Biologists Ltd doi:10.1242/dev.00787 Book reviews Developmental Biology, 7th Edition By Scott F. Gilbert Sinauer Associates (2003) 750 pages ISBN 0-87893-258-5 £37.99 (paperback)

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Page 1: From egg to organism - Harvard Universityoverview of plant development. For those whose primary interest is plant developmental biology, this section may seem to provide too little

5555

The embryo is a remarkable self-assembly machine. From a single cell,the fertilized egg, arises all of thedifferentiated cell types of the body.Embryos unfold in an elegantlychoreographed manner that we strive tounderstand by observing the process,dissecting it into smaller bits, andmucking up the works by expressing toomuch or too little of some protein. Yetthe mystery remains and, as knowledgeand technology advance, we understandmore about the depth of its complexitythan about the process itself.

Given the beauty and intricacy of thedeveloping embryo, it is a loftychallenge to put the current state ofinformation in a form that is bothunderstandable and captures theimagination of students of biology at theundergraduate and graduate level. ScottGilbert has met this dual challenge in thelatest edition of Developmental Biology.He has caught the excitement of the fieldin a remarkably lucid way. The bookstarts by building from first principlesand defining concepts, and then movestoward the details of morphogeneticprocesses themselves and what is knownabout their molecular bases. This bookis worth investing in because it has beennicely expanded and updated over theprevious versions, and also has muchimproved graphics.

Although developmental biology hashistorically deep roots, some of theseminal work of the past is often ignored.Gilbert is keenly aware of this and doesa wonderful job of putting the study ofdevelopmental biology in historicalcontext. He describes the importanceof development for understandingevolution, and discusses how itinfluenced Darwin’s discovery of theorigin of the species. He frequently refersto the work of individuals who pioneereddifferent aspects of experimentalembryology and made pivotal discoveriesthat still influence thinking today. He also

discusses the interesting interfacebetween embryology and genetics, twofields that once were thought of asdifferent disciplines, but that clearly havebecome integral to one another and arenearly indistinguishable today.

The book does a very nice job of lookingat the developing embryo at manylevels, from the submicroscopic to themacroscopic. Given the importance ofregulatory and coding regions of thegenome, and the proteins that theyencode, Gilbert provides an excellentintroduction into the fundamentals ofdifferential gene expression. Heexplains basic concepts in cell biologyand genetics, particularly those that areintegral for developmental biology, suchas cell interactions and cell signaling.Furthermore, there is a broadintroduction to many differentorganisms so that the book does notseem too ‘vertebrate-centric’. Of course,there is more detail and attention givento the better characterized ‘model’organisms, but not at the expense ofkeeping a broad perspective. Sprinkledthroughout the text are excellentillustrations that help the readervisualize the processes under study.

The book is organized into four largesections, each of which is subdividedinto chapters. The first section presentsthe background information that isessential to understanding the conceptsof biology, both historically andscientifically. The second sectiondiscusses early events in development,starting with fertilization andproceeding to axis formation. The thirdsection deals with particular types oftissues, ranging from the formation ofthe nervous system to the limb. Finally,the book ends with a discussion of themedical implications of developmentalbiology and how development caninstruct our understanding of evolutionand vice versa. This section alsoincludes a nice chapter, contributed by

Susan Singer, that provides anoverview of plant development. Forthose whose primary interest is plantdevelopmental biology, this sectionmay seem to provide too little coverageof this topic and to come too late in thebook. It is safe to say that the book ismostly one on animal developmentalbiology.

In conclusion, I highly recommendGilbert’s Developmental Biology tostudents at both the university and post-graduate level. For that matter, it’s avery good read for more advancedinvestigators as well, and is a goodresource for checking up on the latestresearch in an area that is outside of yourown. It is up-to-date and is written inan engaging style that captures theexcitement of developmental biologytoday.

From egg to organismMarianne Bronner-Fraser

California Institute of Technology, Pasadena, CA, USAe-mail: [email protected]

Development 130, 5555© 2003 The Company of Biologists Ltddoi:10.1242/dev.00787

Book reviews

Developmental Biology, 7thEditionBy Scott F. GilbertSinauer Associates (2003) 750 pagesISBN 0-87893-258-5£37.99 (paperback)

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5556 Development 130 (23)

As most of us are aware, today’s primaryschool, high school and undergraduatebiology programs are struggling toincorporate even a fraction of the‘molecular revolution’ of biologicalknowledge and technologies thatsurround us. In the first term alone, lifescience and biology classes of the newmillennia routinely cover condensedversions of the year-long classes taughtin the 60s, 70s and 80s. Teachers nolonger have the luxury of spending halfa year presenting Mendel and his peas.

As many of us appreciate, fruit fliesoffer a superb means to illustrate basicMendelian principles to kids as young asprimary school age. Among modelorganisms used in research, the fruit flyis one of the most thoroughly analyzed,and it is appreciated by geneticists,neurobiologists and developmentalbiologists alike. In addition, flies area practical choice of school andundergraduate teachers because of theirrelative ease of handling, their smallsize, their rapid generation time and, notleast, because of their rich array of easilyscored and provocative mutantphenotypes.

PlayHowever, imagine yourself, if you will,surrounded by 22 eager [read:impatient], inquisitive [read: demanding]and communicative [read: shouting]eleven-year-olds, whilst simultaneouslyhearing: ‘Is this fly a girl or boy?’, ‘Arethese specks pupae or larvae?’, ‘Is thisfly poop?’, ‘My flies are escaping. Arethey going to bite me?’, ‘But Mendelused peas, right?’, ‘Teacher, Sandy’sgonna be sick!’

Stop. Rewind... PlayNow imagine yourself in total control ofthose same 22 eleven-year-olds while all44 eyes are glued to the tube [more thanlikely their favorite activity], with each

of the above mentioned questionsanswered in living color during a 40-minute educational andentertainingCD-ROM entitled Fly Cycle2. Joy!

Fly Cycle 2: the movieFor these reasons, among others, the 40-minute CD-ROM created by Mary Tylerand Ronald Kozlowski, with con-tributions from Rachel Fink, ShinyaInoue, Dan Kiehart, Eric Wieschaus andPaul Young, should become a welcomeand familiar tool for students in biologyand genetics classes at primary schooland high school, and at undergraduateand even graduate levels.

Fly Cycle2 introduces the viewer to thelife cycle of the fly from severalperspectives. First, a section onreproduction provides clear and detailedfootage of adult courting behaviors andmating [teaching aid: tell the kids it’s foradults only]. Second, Fly Cycle2

illustrates beautifully the various stagesof embryonic development, larvalgrowth and metamorphosis. Third, a

number of the mutant phenotypescommonly used in introductoryDrosophila genetics courses aredescribed.

This is not all, the CD-ROM alsoincludes two text files: one thatannotates the movie, and a 40-pagebooklet with additional materials relatedto Drosophila research, instructions forlaboratory studies, a glossary and linksto online study questions. The moviecombined with the 40-page booklet willbe particularly useful in undergraduategenetics laboratories. It will not onlysupplement the student’s materials butwill help teachers design laboratoryexercises that will complement themovie. Undoubtedly, teachers will beable to come up with other creative waysto use and present the informationprovided in Fly Cycle2. Overall themovie is a wonderful contribution to thefield, and will be appealing and useful toa wide audience from primary schoolkids to postdoctoral fellows. However,there is room for improvement, with themain drawback being that it provides toolittle or too much depending on theviewer’s level of knowledge. Forstudents just being introduced to the fly,some parts of the movie are too detailedand their attention spans will be tested(e.g. the level of detail on the first 13embryonic cell cycles will be too muchfor them). However, this same footagewould be highly interesting to advancedstudents. Likewise, the advanced studentwill smile at the more basic footage (e.g.how to distinguish a male from afemale), whereas younger students willfind this most informative.

The target audiences of FlyCycle2 are asdiverse as the field of Drosophilagenetics that it addresses. When makingthe movie, the authors must havestruggled with what to include and whatto leave out. For example, oogenesis, sointensely studied today, is not included

Liz and Norbert at the moviesLiz Perkins 1 and Norbert Perrimon 2

1Pediatric Surgical Research Labs, Massachusetts General Hospital, Charlestown, MA, USA2Department of Genetics, Harvard Medical School, Boston, MA, USAe-mail: [email protected] and [email protected]

Development 130, 5556© 2003 The Company of Biologists Ltddoi:10.1242/dev.00813

Fly Cycle 2

By Mary S. Tyler and Ronald N.KozlowskiSinauer Associates (2003)ISBN 0-87893-848-6 £12.99 (CD)

Page 3: From egg to organism - Harvard Universityoverview of plant development. For those whose primary interest is plant developmental biology, this section may seem to provide too little

Invertebrate animals span a hugebiological realm of form and function,and have evolved many uniquecharacteristics. The wealth of varietywithin this diverse group not onlycontributes to the health of theecosystem, but also provides a virtuallyunlimited potential for biologicaldiscovery. Models for basic researchoriginally included a large number ofinvertebrates. However, over the pastfew decades, most research has focusedon a limited number of systems, such asflies and worms, for which moleculargenetic technology is easily available.Nevertheless, two things have recentlychanged this focus: the development ofRNA interference (RNAi) techniques toperturb gene expression in diverseorganisms and a renewed interest in theevolution of developmental mech-anisms. One main caveat to beinginterested in diverse organisms is thecomparable paucity of technicalinformation regarding the handling oftissues and cells from these organisms.Knowing where to begin with any newanimal system requires a bit of patience,a certain amount of stubbornness, and,now thanks to Mitsuhashi, a good roadmap to plan your way through this newunknown.

For scientists initiating tissue cultureprojects, Invertebrate Tissue CultureMethods starts with a detailedintroduction into the necessary andsuggested equipment needed to properlyequip facilities for invertebrate cultureresearch. General principles forestablishing and maintaining cultures arediscussed, with an emphasis upon thoseareas most likely to delay the progress ofestablishing a viable culture. Althoughmedia selection can partly depend uponempirical determination, several suc-cessful culture solutions are described inthe text, which may serve as a templateto customize media selection for animalsof a specific phyla. In addition, severalsuggested media additives are describedto maintain the proper nutrition andgrowth of the culture. Once a culturemedia has been selected, contaminationof the culture must be avoided; to thisend, frequent sources of contaminationare outlined in this book, such as foodand bacteria in the gut, as well as fromthe incompletely sterilized externalsurfaces of the animal. Avoiding anexcess of unwanted blood, which willoxidize to toxic metabolites, includingmelanin, is another recurring theme inthe initial establishment of a healthyinvertebrate tissue culture.

Tissues of interest are usually bestidentified through careful dissection andconsultation of available anatomicalinformation.Invertebrate Tissue CultureMethods offers a comprehensive arrayof figures, many of which are focused onthe proper identification and removal ofa variety of specific tissues from a widerange of invertebrate phyla: Insecta,Prochordata, Echinodermata, Mollusca,Annelida, Nematoda, Platyhelminthes,Coelenterata, Porifera, and various non-insect arthropods. Although theemphasis of the text is on previouslyreported culture methods forrepresentative members of theseinvertebrate phyla, one can alsoextrapolate these methods to new tissuetypes and organisms. An equally broadportion of the book is devoted to theestablishment of whole-organ culturefor selected tissues from the abovephyla, and this section usefully focuseson those tissues that have beensuccessfully maintained. Techniques forstudying developmental processes inembryonic tissues, as well as in imaginaldiscs and gonadal tissue, are outlined formost phyla, although any given speciesmay not be covered in great depth. Mostmajor organ systems are represented,and are discussed from both a

5557Book reviews

in the current version, nor is therepresented a practical way to handle andperform genetic crosses.

Perhaps one way to sufficiently addressthe needs of each target audience is tothink of the next step: what will FlyCycle3 look like? Our suggestion wouldbe to divide future Fly Cycle3 contentinto sections targeting each audiencelevel. Fly Cycle3 Part 1 could targetyounger students and fly novices, andcould describe the Drosophilalife cycle,sex differences and mating behaviors,as well as explaining salivary glandchromosomes and showing common

genetic mutations. Fly Cycle3 Part 2could target more advanced students(those taking lab classes), and couldinclude basic genetic information likehow to pick virgins, how to make andfollow simple F1 and F2 crosses, and howto clone a gene. Finally, Fly Cycle3 Part3, for the most advanced students, coulddescribe novel visualization methodsusing green fluorescence proteins tofollow specific developmental processes,and could include descriptions of variousgenetic technologies used in researchtoday.

Stylistically, the movie could be

improved with a more energeticnarrative and, particularly desirable,pauses between sentences and subjects,as well as more pointers/arrows to directthe viewer’s attention to the structuresbeing described. Finally, although thereis a terrific introduction in the movie, theending is too abrupt and a summarywould be helpful.

Nevertheless, we give Fly Cycle2 twothumbs ups, we highly recommend itand we look forward to Fly Cycle3. Asfar as we are concerned, this educationaltool should be promoted, made widelyavailable and developed further.

Spineless culturePaul A. Sykes 1,2 and Barry G. Condron 2,*1Medical Scientist Training Program, University of Virginia, Charlottesville, VA, USA 2Department of Biology, University of Virginia, Charlottesville, VA, USA*e-mail: [email protected]

Development 130, 5557© 2003 The Company of Biologists Ltddoi:10.1242/dev.00800

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5558 Development 130 (23)

developmental and a functionalperspective, including the nervoussystem, the circulatory system andhemocytes, intestinal tissues, andspecies-specific exocrine tissues (suchas silk and pheromone glands). Once theappropriate tissues have been removed,there are a number of general methodsin cell culture described that can beapplied to fit individual experimentaldesign, including protocols for cellulardissociation, subculture and theinduction of cell growth.

The concluding portion of InvertebrateTissue Culture Methods focuses onrelated techniques for the study of cellsin culture. These instructive chaptersoffer general directions for thecharacterization and manipulation ofviable tissue culture. Broadly, thesechapters describe the genetic identi-fication of cell lines, methods to evaluateand document cell growth and viability,techniques for optimal photography, andtips for creating large-scale invertebratetissue cultures. This final section offers aconcise compilation of several modernand traditional approaches to the

characterization of cell culture, and isoutlined in a protocol-driven style that isaccessible and easily followed. Anappendix is provided to the main text,listing the various formulations of media,as well as media suppliers, together withan anthology of previously reportedcontinuously cultured cell lines.

There are a number of places where thisbook could have been improved. Whilean outline of basic cell culture andsterile techniques will prove useful tothe uninitiated researcher, in reality, thisintroductory section could have beenreplaced with a reference to any of anumber of standard cell culturehandbooks. In addition, the section onorgan culture could have been expandedto focus on the techniques that currentlyapply to flies, as the myriad oftechniques developed for flies willequally apply for other organisms. Evena table of references for additional flyorgan culture protocols would have beenuseful. Also, the book was short ondescriptions of molecular technologies,and this aspect could have beendeveloped to cover techniques such as in

situ hybridization and, in particular, theuse of RNAi. However, overall this bookwill prove to be an essential companionto any laboratory wishing to researchnon-standard invertebrates.

One of the most exciting features of thisbook is the new opportunity for discoverythat will accompany the reading of thistext, and while it could certainly be usedas a teaching device in a formallaboratory setting, it is also suited forhands-on use in any invertebrate researchlab. As scientific questions ofdevelopmental and evolutionary interestcontinue to probe invertebrate systems,researchers are likely to continue torequire a broad source of species-relevantinformation, and, to this end, InvertebrateTissue Culture Methodsprovides anexcellent resource.

All animals, including humans, beginlife as a single cell. During the first fewhours of development, that initial celland its progeny make a series of crucialdecisions that ultimately lead to theformation of organs and structures of theadult organism. The principal aim ofdevelopmental biology is to understandhow these amazing processes occur.

In the past two decades, the explosion ofinformation and novel techniques inmolecular biology and genetics hasarmed modern embryologists withpowerful tools with which to dissect themolecular basis of development. Recentstudies have illustrated a remarkableconservation of molecular and cellulardevelopmental strategies among embryosof different species. The future of

developmental biology therefore relies ona comparative approach, especially in thepost-genome era.

Molecular Principles of AnimalDevelopment stands perfectly withinthis context. Martinez Arias andStewart’s rationale is to approachdevelopmental biology, primarily froma molecular perspective. Thus far,traditional textbooks have begun with adescription of developmental processes(such as axis formation, gastrulation andorganogenesis) in different modelsystems. Molecular explanations weresubsequently provided along the way. InMolecular Principles of DevelopmentalBiology, however, molecules take centerstage rather than the embryo or itsconstituent parts.

The book is split into three sections.After a general introduction about thefundamental questions of develop-mental biology over the past fewcenturies, chapters 2-5 provide a basiccourse of molecular biology surveyingtopics such as transcription, signalingmolecules and receptors, signalingpathways, and networks. These fourchapters should give the reader thetools to understand the molecularmechanisms underlying developmentalevents. It is hard to predict, however, ifthis general overview is rigorousenough to teach a molecular under-standing of development to a readerlacking any previous background inmolecular biology or genetics. The nextsection, chapters 6-9, describes theintegration of basic molecular

Molecules take center stageFrancesca M. Spagnoli and Ali Hemmati-Brivanlou*

The Rockefeller University, New York, USA*e-mail: [email protected]

Development 130, 5558© 2003 The Company of Biologists Ltddoi:10.1242/dev.00657

Invertebrate Tissue CultureMethodsBy Jun MitsuhashiSpringer-Verlag (2002) 446 pagesISBN 4-431-70313-6£70.00/$119.00 (paperback)

Page 5: From egg to organism - Harvard Universityoverview of plant development. For those whose primary interest is plant developmental biology, this section may seem to provide too little

5559Book reviews

mechanisms into cellular anddevelopmental processes such as celladhesion, polarity, movement, celldivisions or cell death. Finally, the lastthree chapters focus on selected topics:how specific cell types are generated(e.g. myogenesis, neurogenesis); andthen how specific cell types becomeorganized in two- or three-dimensionalpatterns (e.g. development of theC. elegans vulva, vertebrate limbdevelopment, patterning and growth ofthe Drosophilawing).

The final challenging aim of the book,which is very valid, argues for theneed to re-interpret all the develop-mental processes within a molecularframework. The amateur embryologist,however, might be better served with abroader view of events that graduallyfocuses at the molecular level. Forexample, it is useless to build up agene map of embryos without having aclear concept of the fate map and the

ability to correlate gene expressionwith the spatiotemporal coordinates ofthe embryo. The Wnt signalingpathway, for example, can exertopposite effects depending on whereand when the embryo is exposed to it.

In conclusion, this textbook should beconsidered as a companion to moretraditional texts about developmentalbiology, and it is clearly useful foradvanced graduate students and teacherswho already have a background ofembryology. Readers will further benefitfrom the figures and suggested readings.Ultimately, however, we should leavethe embryo on the center stage and buildup the molecular networks around it.What matters at the end, is not only theunderstanding of the molecularcomponents, but the overall strategiesthat an embryo uses to guide its owndevelopment.

Molecular Principles ofAnimal DevelopmentBy Alfonso Martinez Arias and AlisonStewartOxford University Press (2002) 424 pagesISBN 0-19-879284-0£29.99 (paperback)

Zebrafish are easy and inexpensiveto maintain, their embryos aretransparent, and their genetics tract-able. Thus, they have become a power-ful model with which to investigate anenormous variety of problems inbiology and medicine. As an exampleof their increasing popularity, over thepast decade the number of zebrafishpapers listed on PubMed has increasedby over tenfold. With increasedpopularity comes increased diversity inthe organ systems and cell biologicalprocesses under study. Until now, toobtain a comprehensive view ofzebrafish biology the only sourceswere: the scientific literature, which isvast and not easily traversed withoutexpert guidance; The Zebrafish Book,which needs updating; and theCompany of Biologists Zebrafish CDROM, which is permanently stuck in1996.

Fortunately, there is hope in the form ofa new book, Pattern Formation inZebrafish, which goes a long waytowards helping the uninitiated tounderstand why zebrafish have madesuch great strides. The editor, LiliannaSolnica-Krezel, was instrumental in theidentification of many of the mutationsdescribed in the book. She has enlistedsome of the top names in the zebrafishcommunity to contribute theirperspectives on zebrafish development.Although the book largely focuses onthe control of early development, italso features discussions on thedevelopment of several key organsystems.

There is something here for everyone.For the embryologist, the first half of thebook is a real treat, giving up the secretsof the molecular events underlying axisspecification, germ layer identity and

gastrulation movements. Each chapterprovides explanation in clear accessibleterminology with the salient pointsreiterated by the various authors, so thatthe reader will remember what one-eyedpinheadis (for example), what it does,and why that name is appropriate andhelpful. For the neurobiologist, therelative simplicity of neurogenesis, tractand commissure formation, and neuralcrest diversification makes it easier tounderstand the homologous eventsin higher vertebrates. For thecardiovascular aficionado, mysteriessuch as the complex morphogeneticmovements underlying heart formation,the physiology of heartbeat and thespecification of venous versus arterialfates all become more understandable.There is much more and all of it is good.In general, the reduction of complexprocesses to the molecular detail makefor exciting reading.

Watering down vertebrate developmentDerek L. Stemple

Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK e-mail: [email protected]

Development 130, 5559© 2003 The Company of Biologists Ltddoi:10.1242/dev.00656

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5560 Development 130 (23)

I found three aspects of the booklacking, however. First, I feel the priceis far too high. This is likely to limitsales of what is otherwise an excellentbook. Graduate students, who wouldbenefit most from the book, willprobably find it unaffordable. Second,there are some notable absences in thebook. The recent genetic work onear development in zebrafish hasuncovered new aspects of themechanical basis of hair-cell function

but it is not discussed at all. Mypersonal favourite embryonic structure,the notochord, is essential forvertebrate development but is onlymentioned in passing and then only inthe context of other systems. Finally, Ifound the index to be incomplete andthus not very useful. There are manyexamples of gene or mutant nameswhere only a few of the citations arelisted in the index. These minorcriticisms aside, I think the book is

extremely helpful and expect mostzebrafish laboratories will want to havea copy close at hand.

Pattern Formation inZebrafishEdited by Lilianna Solnica-KrezelSpringer-Verlag (2002) 438 pagesISBN 3-540-43576-X£139.50/$225.00 (hardback)

The field of evolutionary developmental(evo-devo) biology is populated withscientists from diverse disciplines whoare seeking the answers to questions thathave been asked for millennia: why doorganisms look different, how are theseorganisms built, are there commonthemes to how they are built, are thererules governing the evolution oforganismal form? The surprise of evo-devo over the last few decades is that areductionist approach, molecular devel-opmental genetics, has repeatedlydetermined that the same genes areinvolved in building divergent organ-isms. One might decide thereforethat morphological evolution is nowunderstood: it is ‘simply’ the evolutionof regulation of a conserved ‘tool box’of genes combined with rare butimportant events like gene duplicationand changes in protein function. It iseasy to get caught up in recent progresstowards explaining diversity at themolecular level, and to forget, therefore,how much of diversity remains un-explained and how instead of answeringmany questions about biologicaldiversity we have simply failed torecognize them as problems.

We should therefore welcome attemptsto bring our attention to broader themesand overlooked issues. This is just whatAlessandro Minelli attempts to do formacro-evolutionary questions in his

recent book The Development of AnimalForm: Ontogeny, Morphology, andEvolution. Minelli seeks a unificationof evolutionary and developmentalbiology, and believes that this requires aphilosophical shift by participants inevo-devo. He encourages workers toview the entire life cycle as develop-ment, not just the embryonic patterningphases, and to keep in mind thatselection acts upon all these stages, notjust upon the final adult form. This is atruism for evolutionary biologists, butperhaps a novel perspective for somedevelopmental biologists. Minelli alsoquestions the prevalence of what he calls‘finalism’ in developmental biology, orthe idea that all of development isdirected towards the goal of producingthe adult form. He points out that welong ago shed the notion that animalsevolve inexorably towards ‘higher’forms. Why haven‘t developmentalbiologists recognized, therefore, thatdevelopment is not goal directed? I‘mnot convinced that this analogy is aptand I‘m also not convinced that suchfinalism is common in developmentalbiology. Open the pages of anydevelopmental biology journal more orless at random and you will find researchdelving into the details of developmentalmechanisms, often with little concernfor the consequences for the adultphenotype. There may, however, be agrain of truth in Minelli’s criticism. Evo-

devo workers have been quick to inferorgan homology from a few embryonicgene expression patterns. It is now clearthat such comparisons, even when theyinvolve more than just a few expressionpatterns, are fraught with difficulty,particularly when they are performedin the absence of phylogeneticinformation.

Minelli is also concerned that most ofthe experimental knowledge used toaddress evo-devo questions is derivedfrom studies of a handful of modelsystems. There is, however, everyindication that investigators willcontinue to expand the list of animalsunder study and that tools are beingdeveloped for functional assays in ‘non-model’ organisms. So I view Minelli’sconcern as a short-term issue. None-theless, he points out a number ofunusual phenomena in little-studiedanimals and these ‘exceptions’ mayprovide key insights into the ‘rules’ ofevo-devo.

Minelli revisits several subjects he haspublished on elsewhere, includingparamorphism (the idea that limbs arein some way homologous to the mainanteroposterior body axis), and variousconcepts related to segmentation,including the idea that segments are notonly made in different ways betweentaxa but also within a species. I found

What you didn’t know about evo-devoDavid L. Stern

Department of Ecology and Evolutionary Biology, Princeton University, NJ, USAe-mail: [email protected]

Development 130, 5560© 2003 The Company of Biologists Ltddoi:10.1242/dev.00767

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5561Book reviews

the chapter on segmentation the mostfrustrating because I could not get aclear grasp of how Minelli’s conceptsdiffered from our current understandingof segmentation in Drosophilaandvertebrates. Minelli introduces theconcepts of holomeric segmentation,which produces ‘true’ segments(eosegments), and meromeric seg-mentation, which produces seg-mentation within an eosegment.However, Minelli writes ‘This is not theplace for reviewing in detail themechanisms by which segments aremade in annelids, arthropods, andvertebrates’ (p. 195). Where is theplace, then? What precisely is therelationship between the Drosophilasegmentation cascade, and eosegmentsand merosegments? This is an extremeexample of Minelli’s conversationaltone. Those who already understand themolecular genetics of segmentationand the terminology associated withsegmentation in comparative morph-ology may find gems in this chapter.The rest of us are left out in the cold. IfMinelli wants evo-devo biologists –who traditionally have either a strongbackground in development or inevolutionary biology – to sit up andtake notice, then he needs to make theconnections more clearly.

This is not a text for undergraduates, andI suspect that many readers, particularlythose with poor training in eitherdevelopmental biology or comparativezoology, will be lost in places. Forexample, Minelli refuses to explain

many of the developmental argumentsthat require a thorough prior under-standing of the contemporary develop-ment literature. He writes ‘There is noneed to…explain the concept of the Hoxcode…or to discuss colinearity’ (p. 47).Although most students trained indevelopmental biology won’t needthis explanation, most trained inevolutionary biology will. The reversemay be true for the comparative

morphology terminology scatteredthroughout the book, although I fear thatmost students trained in contemporaryevolutionary biology will be morefamiliar with models of linkagedisequilibrium than with theterminology of comparative morph-ology (I speak from experience). Thefigures are poorly labeled and willconfound those with a limited training incomparative morphology. I found anumber of errors of citation for theliterature I know, which made me waryof the remaining citations.

My overall impression of the book isthat it is like having a conversation withthe author. He touches upon manyissues that he has clearly thought aboutdeeply and scatters provocative ideasthroughout the text. Every time Istarted getting lost in the ideas, hethrew in a fascinating example; everytime I lost track of the examples, hethrew in a surprising idea. These ideasand examples are not always clearlyconnected and the arguments are nottightly argued, but the book wraps upwith a satisfactory summary that, inmy view, should have been theintroduction. The book raises far morequestions than it answers (I’m not sureit answers any), but that appears to havebeen Minelli’s goal. For the preparedmind, and the mind prepared to focuson essentially macro-evolutionaryissues, this is a worthwhile con-versation with Minelli.

The Development of AnimalForm: Ontogeny, Morphology,and EvolutionBy Alessandro MinelliCambridge University Press (2003) 342 pagesISBN 0-521-80851-0£55.00/$75.00 (hardback)

‘Life forms illogical patterns. It ishaphazard and full of beauties which I tryto catch as they fly by, for who knowswhether any of them will ever return?’

I doubt the dancer Margot Fonteyn wasever a student of developmental biology;however, if she was, she would have

appreciated that vertebrate embryonicdevelopment is a truly mesmerizing andbeautiful process.

In Patterning in Vertebrate Develop-ment, Cheryl Tickle has compiled acomprehensive account, contributed bywell-known developmental biologists,

that provides a fascinating insight intothe complexity of vertebrate develop-ment and the consequences of patterninggone awry. Each chapter focuses onseveral species and emphasizes therecent genetic discoveries that underpinthe molecular basis of vertebratepatterning. Patterning is the mechanism

Vertebrate patterning: how to cross-stitch an embryoPaul Trainor

Stowers Institute, Kansas City, MO, USAe-mail: [email protected]

Development 130, 5561© 2003 The Company of Biologists Ltddoi:10.1242/dev.00696

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that coordinates cell position,proliferation and differentiation duringembryogenesis, and is mediated bycell signaling interactions, of whichmorphogen gradients are of keyimportance. This complex mechanismensures that characteristic features suchas the head, limbs, nervous system,organs, and even individual cartilageand bone elements, such as thevertebrae, develop in the correct locationwith the appropriate size and shape.

One of the major questions indevelopmental biology is how cellsacquire positional information. It istherefore very fitting that the openingchapter of the book introduces us tomorphogen gradients and the conceptthat cells acquire positional informationbased on their abilities to respond todifferential levels or thresholds of asignaling gradient. This provides theperfect introduction to the chaptersthat follow, which can be broadlycategorized into three themes: (1) bodyaxis and mesoderm patterning; (2)central and peripheral nervous systemdevelopment; and (3) limb andevolutionary development.

What is clear in each section is theunderlying importance of morphogengradients and the reiteration of similarsignaling pathways in quite distinctdevelopmental processes. For example,the second chapter describes estab-lishing the vertebrate body plan andhighlights the fact that despite thesignificantly distinct geometry andmorphology that exists between frogs,fish, mice and birds, the determinationof polarity and the process ofgastrulation are remarkably similar. Itwas Lewis Wolpert who famously andappropriately said, ‘it is not birth,marriage, or death, but gastrulation,which is truly the most important timeof your life’. To any embryo, the failureto gastrulate properly is terminal.Following on from gastrulation, themesoderm theme continues with theexploration of somite and axialdevelopment, and in particular discusseshow a genetic oscillator patternsunsegmented mesoderm into somiteblocks. We also learn how somitesdifferentiate to give rise to a reiteratedpattern of vertebrae and muscles andhow these are specified in an

anteroposterior fashion primarily by theHox genes.

By far the largest section of the bookdescribes the patterning of the nervoussystem. The importance of a coordinatedintegration of positional information isno better illustrated than in the complexdevelopment of the adult central andperipheral nervous systems. Beginningwith a chapter on neural competence andneural plate induction, we then discoverhow the neural plate becomesregionalized both anterioposteriorly anddorsoventrally in response to localsignaling gradients. This is augmentedby a discussion of the mechanisms thatcontrol axon guidance, which ultimatelyprovides the essential scaffolding uponwhich the elaborate cytoarchitecture ofthe brain and spinal cord aresuperimposed.

The remaining one-third of the book,which I particularly enjoyed, coversthe migration and patterning ofneural crest cells, as well as limbpatterning, and is rounded off by afinal chapter that describes theimportance of these tissues invertebrate evolution. Neural crestcells give rise to an enormousnumber of cell types, tissues andorgans during vertebrate develop-

ment, and are synonymous withcraniofacial evolution and thetransition from a sessile to apredatory lifestyle. Similarly, theformation of paired fins and tetrapodlimbs helped to usher the vertebrateinvasion of land, and we arebeginning to understand the geneticbasis of the distinction betweenforelimbs and hindlimbs. Fittingly,the final chapter on the evolution ofvertebrate patterning describes thesemajor evolutionary transitions andreinforces many of the ideas thatarise in the preceding chapters onneural crest cell and limbdevelopment. This chapter alsotouches on distant extant vertebraterelatives, such as amphioxus,lampreys and ascidians, all of whichhave contributed enormously to theunderstanding of vertebrate evolutionthrough studies of comparativegenetics and anatomy.

The trouble with any book these daysis that the field of developmentalbiology is moving so rapidly thatmany ideas become outdated orsurpassed very quickly. For example,there appears to be increasingevidence that a link might existbetween the oscillator or somite-clockmechanism and Hox gene patterning,which might facilitate the co-ordination of body plan segmentationwith anteroposterior patterning. Thisrecently emerged topic is discussedonly briefly in this book. Similarly,the field of neural crest cell andcraniofacial development has hotlydebated whether cranial neural crestcells act cell autonomously or areplastic and responsive to theenvironment; the current consensus isthat both mechanisms play importantroles. This debate is also only brieflytouched upon in this book, as theneural crest chapter mainly covers thedevelopment of the trunk neural crest.Overall, however, this book providesa concise yet comprehensive insightinto the major events that occurduring vertebrate embryonic pattern-ing and should prove to be a valuableresource for researchers and the moreadvanced students of developmentalbiology.

Patterning in VertebrateDevelopmentEdited by Cheryll TickleOxford University Press (2002) 228 pagesISBN 0-19-963870-5 (hardback) ISBN 0-19-963869-1 (paperback) £80.00 (hardback)/£40.00 (paperback)

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5563Book reviews

A six-layered cerebral cortex is auniquely mammalian structure and is thecenter of cognitive function. Theprocesses and genetic controls thatgovern its development are subjects ofintensive study and have captured theattention of many developmentalbiologists. One major goal in this fieldis the identification of the factors andpathways that control the generation ofprecise numbers of the principal celltypes within the cerebral cortex:neurons, oligodendrocytes and astro-cytes. A second major goal is tounderstand how these building blocksare targeted to the different structureswithin the cortex, and how they areinterconnected to establish functionalnetworks.

The understanding of the ontogeny ofthe cerebral cortex requires us tounderstand not only how this structure isbuilt in a step-by-step fashion, but alsohow this innate program is designed tointeract with environmental influencesto promote plasticity. Although this is animmense challenge, we need to have afull understanding of the developmentalprogram of the cortex in order to gain anappreciation of how we think. To borrowa commonly used phrase, understandingthe cortex is to understand how weunderstand.

Cortical Development. FromSpecification to Differentiationpresentsa concise description of several of thekey steps that occur during thedevelopment of the cortex. This is thefirst volume to be published in a two-volume set and concentrates on ‘early’events in ontogeny – issues relating tocortical cell generation/specification,migration and early differentiation. Inthis volume, Hohmann has selected across-section of what she and many inthe field would consider to be the mostpertinent and exciting areas in currentresearch on cortical ontogeny.

The book is divided into eight chapters,which have been written by differentexperts in the field and build upondifferent themes following a more-or-less temporal course through corticaldevelopment. Richard Nowakowski etal. beautifully summarize years ofcollaborative work on the develop-mental dynamics of cell proliferation inthe cortex. This work led to several keyadvances in the field, including thedescription of cell cycle regulation in thegeneration of cortical cells. MarkMehler, in the first of two chapters thathe contributes, focuses on mechanismsof lineage diversity and the role of thebone morphogenetic proteins, fibroblastgrowth factors (particularly FGF2),sonic hedgehog and basic helix-loop-helix molecules in this process. In hissecond chapter, he studies regionalpatterning and neural subtypespecification under both morphogen andtranscriptional regulation. Thesemechanisms serve to create thenumerous distinct types of cells thatconstitute the cortex, and we learn of therelationship of these pathways toneurodegenerative diseases.

Later events in cortical development arecovered in the subsequent chapters. Forexample, Bernd Sutor discusses gapjunctions and their possible role inestablishing early neuronal circuits,while Marcin Gierdalski and SharonJuliano provide an overview of neuron-glial interactions and their role inneuronal migration. This chapter alsocovers the reeler pathway (in whichreelin is secreted from a small group ofcells and influences migration of most orall neurons arriving in the cortex), aswell as the authors’ own work on themethylazoxy methanol (MAM) model ofcortical dysplasia, and its relevance tothe reeler pathway. Several of thesechapters also discuss the processes andmolecules that are important for synapticdevelopment and cortical plasticity.For example, A. Kimberly McAllister

discusses neurotrophins and their role indendritic growth and synaptic plasticity,and Alvin Lyckman and Mriganka Surdiscuss neuronal re-wiring plasticity in afascinating model in which the visualinput fibers of a ferret are re-routed to theauditory processing centers. In thismodel, ferrets are capable of using there-wired auditory cortex to respond tolight as a visual, rather than as anauditory, stimulus. The molecularcharacterization of this model and itsfuture downstream applications, such asstrategies to identify differential geneexpression, are discussed. The relevanceof the immediate-early genes [such asactivin, NARP (neuronal activityregulated pentraxin) and homer], whichare activated by an initial cascade of geneexpression that is triggered by anextracellular signal, are also discussed inthe context of synaptic development andcortical plasticity by Katrin Andreassonand Walter Kaufmann.

Increasingly, successful inquiry in theneurosciences depends on stronglyinterdisciplinary approaches. Theinterdisciplinary nature of the chaptersis one of the great strengths of thisbook. However, there is little inter-relatedness or synergy developedbetween many of this book’s chapters,despite there being much repetitionbetween many of them. That said, eachindividual chapter does stand alone andprovide a detailed view of the role ofeach of the highlighted molecules andpathways in the construction of thecerebral cortex. Neurodevelopmentalbiologists may also notice that there isa paucity of loss-of-function data that iscustomarily used to support the types of

Building a better brainJoseph G. Gleeson

University of California, San Diego, La Jolla, CA, USAe-mail: [email protected]

Development 130, 5563© 2003 The Company of Biologists Ltddoi:10.1242/dev.00754

Cortical Development. FromSpecification to DifferentiationEdited by Christine F. HohmanSpringer-Verlag (2002) 181 pagesISBN 3-540-43436-4£76.50/$129.00 (hardback)

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Writing a textbook on developmentalbiology is, today, a dangerous task. Theamount of data being produced in labs allover the world overwhelms every effortto be up to date, or to be fair to everydevelopmental biologist in the business.Today, the study of developmentalbiology entails a vast array of conceptualframeworks, methodologies and explor-ation tools, making it all but impossibleto cover ad extenso the sources,applications and directions of research.As a result, textbooks on developmentalbiology, while trying to cover as muchground as possible, have to focus onsome specific issues. The convergence ofgenetics and embryology on the keyproblems faced by developmentalbiologists makes both disciplinesabsolutely necessary in an entry-levelbook such as this one. A winning bookalso has to look at mechanisms thatbridge genetics and embryology to showhow regulatory gene networks relate tocell biology, hint at the relationshipbetween development and evolution, anddemonstrate the richness of the interfacebetween development and other sciences,such as mathematical modeling.

This is the case with Principles ofDevelopment. The first striking aspect ofthis book is its impressive list of authors– scientists who have all beeninstrumental in shaping the basicresearch and fundamental findings thatcomprise the core of developmentalbiology today. Equally impressive is thelengthy and astonishingly authoritativelist of chapter editors, although, asLewis Wolpert admitted, “I did all thewriting”, while his co-authors were in

“permanent consultation”. The presentbook is a second edition (the first editionwas published in 1998) that includessome crucial findings from the past fiveyears. Needless to say, the first edition,along with the now classicDevelopmental Biologyby Scott Gilbert(Sinauer Associates), has played afundamental role in introducing collegestudents to the difficult issues andproblems that face our science.

Content of the bookThe structure of the book is logical, muchlike the acute mind of its main author, asthose who are lucky enough to knowLewis are well aware. It moveseffortlessly from the general to thespecific and back to the general,reminiscent of the harmonious deploy-ment of a Mahler symphony. Principles ofDevelopmentis divided into 15 chapters.Opening with a short history on thebeginnings of the field, it then delves intothe vertebrate, invertebrate and plantmodel systems that are used in everydayresearch, and provides a shortintroduction into gene identificationprotocols. Next come chapters dedicatedto early pattern formation events invertebrates (particularly frogs, chicks andmice); Chapter 3 takes us through bodyaxes and the formation of the threemetazoan embryonic layers, endoderm,mesoderm and ectoderm, and Chapter 4digs a bit deeper into mesodermpatterning events and the formation of theneural system. Chapters 5 and 6 aredevoted to invertebrate embryogenesis,and review the most important modelsystems: the almighty Drosophila

melanogaster(which has been given, andno doubt deserves, the whole of Chapter5 as a result of its fundamental role inhelping to attain our present knowledge ofdevelopmental processes) and those otherheroes of experimental lore, nematodeworms, sea urchins, ascidian tunicates andslime molds. Chapter 7 outlines theexciting world of Arabidopsis thalianaand plant development in a concise, albeitvery pedagogic, manner.

An excellent entry point into the genericprocesses of development is provided by

5564 Development 130 (23)

arguments that are presented in this text.An uninitiated developmental biologistmight therefore choose a textbook thatprovides a broader view of these events.In addition, the emphasis on synapticplasticity in the later chapters doesnot dovetail well with the issues of

embryogenesis that are presented in thebook’s earlier chapters.

These minor criticisms aside, this bookhelps fill a void in developmentalneurobiology by providing a startingpoint for researchers and for other more

advanced students who are in search ofan update by authorities of the field ofcortical development. It will also help toeducate the reader on a number ofdifferent specialties that are key tounderstanding the pathways thatunderlie the building of the brain.

Embryos at the core of lifeDiego Rasskin-Gutman and Juan Carlos Izpisúa Belmonte

The Salk Institute for Biological Studies, La Jolla, CA, USAe-mail: [email protected] and [email protected]

Development 130, 5564© 2003 The Company of Biologists Ltddoi:10.1242/dev.00860

Principles of Development,2nd EditionBy Lewis Wolpert, Rosa Beddington,Thomas Jessell, Peter Lawrence,Elliot Meyerowitz and Jim SmithOxford University Press (2001) 568 pagesISBN 0-19-879291-3 £31.99 (paperback)

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5565Book reviews

Chapters 8 and 9, which discuss themorphogenetic processes and celldynamics that generate form and celldifferentiation, and the molecularmechanisms that underpin cellspecialization in the embryo. In Chapters10 and 11, the book moves on to thespecifics of structure formation in chicklimbs, the nematode vulva, insect wingsand legs, and internal vertebrate organs,such as the heart, lungs, kidneys andnervous system. Chapter 12 describesthe formation of germ cells and themechanisms of sex determination, aswell as the details of fertilization events(one wonders why this chapter is almostat the end of the book!). Chapters 13 and14 deal with the important issues ofregeneration and growth, issues that,today, touch upon the very hot topic ofstem cell research. The closing chapterattempts to bring together two often-separated issues in modern biology:development and evolution. However,this last topic could have been coveredmore extensively to explain to studentshow development can help in explainingthe origination of novel features inevolution, which is the last bone ofcontention used by creationists tocriticize evolutionary theory.

In summary, this excellent book coversmost of the recent findings and generalknowledge of current developmentalbiology. Perhaps a whole chapterdedicated to theoretical concepts andmathematical modeling could have beenadded, as this would have provided anentry point to those rare, but muchneeded, students who want to ventureinto cross-disciplinary roads. Subjectssuch as bioinformatics, tissue en-gineering, and mathematical modelingof regulatory gene networks and cellulardynamics would also have very muchenriched the contents of the book.

The principles of developmentAn interesting paradox lies at the heartof the discipline of developmentalbiology. On the one hand, there is anemphasis on genes as the controllingoperators of development. On the otherhand, there is an explicit recognitionthat cells are the actual ‘units ofdevelopment’ and that cell behaviorprovides the crucial link between genesand development. Wolpert introducesthe concept of ‘luxury’ proteins as those

that are specific for cell types, but howdoes a knowledge of these proteinsfurther our understanding of embryo-genesis? By focusing our attention onthese genes and proteins we reduce thewhole of developmental biology to‘differentiation’, a narrow path indeed.Instead, the truly important question wemust ask in development is aboutgeneric cell behavior. How do genes andproteins affect cell proliferation, cellgrowth, cell migration, cell adhesion andcell death? From here, the next bridge tocross is that of the generic propertiesof embryonic tissues. How does cellbehavior determine the making ofepithelia, of mesenchyme, of sheets, oftubes or of vesicles? Only then can webegin to understand how organismsdevelop.

Wolpert, along with his high-profileeditors, certainly recognizes theseissues. Principles of Developmenttrieshard to provide an array of specificanswers to all of these issues, butsometimes from questions that are toogenocentric. Development is not onlyabout how the genotype controls thephenotype, but also about howinformation deploys and increases fromrather meager information units, such asgenes, into the rich complexity of adeveloping embryo. Despite an explicitdefinition of developmental biology as adiscipline that “deals with the process bywhich the genes in the fertilized eggcontrol cell behavior in the embryo andso determine its pattern, its form, andmuch of its behavior”, Wolpert’sscientific career has been built upon therecognition that many interacting forcesare at play during development and thatthe emergence of new levels ofcomplexity act together to shape theorganism.

For example, Wolpert’s positionalinformation and gradient formationmodel can be found several timesthroughout the book as it applies todifferent scenarios (e.g. the response ofectodermal cells to activin, thedevelopment of anterior structures inDrosophila as a response to bicoid,or the formation of compartmentboundaries, to mention just a few). Theestablishment of these gradientsdepends upon many interacting factorsinvolving the cell and its environment. It

is the appearance of these and manyother complex interactions that preventsdevelopment from being treated in agenotype-specifies-phenotype fashion.

Thus, the introductory chapter warnsagainst taking genes as the ultimatecause of development, and on page 15we find the following illuminatingcomment:

“…gene expression is only the first stepin a cascade of cellular processes thatlead via protein synthesis to changes incell behavior and so direct the course ofembryonic development. To think onlyin terms of genes is to ignore crucialaspects of cell biology, such as changein cell shape, that may be initiated atmany steps removed from gene activity.”

Indeed this is the case: much musthappen from the moment a gene isexpressed to the actual formation of anorgan. Inside the cell cytoplasm,molecular interactions exhibit complexdynamics, including positive andnegative feedback loops, oscillatoryphenomena and cooperative enzymaticactions. Most importantly, cells acttogether and in coordination to exhibitemergent behaviors that cannot bededuced from the molecular interactionsof the individual cells. Again, Wolpert isnot taken off-guard, a great deal of thesefascinating issues are delivered inChapters 8 and 9, with an emphasis inlinking morphogenetic processes tointracellular molecular interactions. Theold search for how the linearinformation encoded in DNA specifies athree-dimensional organism needs to betransformed into a search for how thelinear information of DNA is translated,reprocessed and spatio-temporallydeployed across network levels (mol-ecules, cells, tissues, organs, the wholeembryo) into a three-dimensionalorganism. Textbooks about develop-mental biology need to emphasize this ifwe want to educate a new generation ofdevelopmental biologists that are able tobring more integrative views to ourscience.

Textbooks a thing of the past?If writing a textbook these days is adangerous task, then reading it, andporing over its sections and subsections,headings and definitions is an act of love.

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I remember my excitement at openingthe first edition of Manipulating theMouse Embryoin 1986. I had justestablished my own transgenic mousecolony in Boston and was strugglingwith problematic animal-housingarrangements, cumbersome genotypingtechniques and a skeptical reviewer ofour first paper on the subject (“this studymerely confirms in vivo what theauthors have already demonstrated incell culture”, the curmudgeon wrote).The technology was still in its infancy,and far from routine for an aspiringtranscription factor jock like myself, butthis book provided detailed instructionson how to address all the burningquestions I had about mouse develop-ment, and validated my tentative plansto extend my previous studies of generegulation using recombinant DNAtechnology. The secrets of mammalianembryogenesis were finally accessibleto molecular biology, no matter what mygrumpy reviewer thought.

The Year of the Mouse Genome, 2003,is an auspicious launch date for the latestedition of this inspirational laboratoryresource. Long regarded as a living bibleof mammalian embryonic manipulationtechniques, the updated third editionfulfills this mandate. It has beencompletely reorganized and expanded inthe talented hands of the new authors,all leaders in the fields of mousedevelopment and genetic manipulation.Andras Nagy and Marina Gertsensteinhave championed chimeric analysis in

mouse embryogenesis, and are knownfor their collective expertise inconditional regulation of the mousegenome. As former head of the mousetransgenic core facility at EMBL,Kristina Vintersten has years of hands-on experience, and is a trusted authorityon the nuts and bolts of mousemanipulation. And Richard Behringer, arenowned mouse geneticist, adds hisprofound knowledge of mammaliandevelopment to the mix. It’s a greatteam.

At 764 pages, this tome is half again thesize of its predecessor, and is burstingwith fascinating concepts and clevertechniques. The excellent historicalbackground chapter has been retainedand updated, as has the one on mousedevelopment. Chapters covering thebasics of transgenic mouse production,embryonic stem cell handling andgenetic manipulation have beenexpanded, and state-of-the-art protocolsare presented in an accessible stylewith more extensive troubleshootingsections. For fields in which significantadvances have been made, such as inimprinting, the sections have beenextended accordingly. The chapter onchimeras has been broadened and makesthe technique seem readily accessible.My lab has never made a chimera but, asI read, I found myself thinking of themany ways I could use this approach.

An impressive amount of new materialhas been added as well. Explanatory text

and figures reveal the trade secrets ofmouse cloning, assisted reproductionstrategies (including intracytoplasmicsperm injection and in vitro fertilization)and whole embryo culture systems.Other novel features include DNAelectroporation and reporter geneexpression in living embryos, the uses ofplastic casting to capture morphologicalanomalies, and other techniques for

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It strikes us as something from a past,romantic era – hardly 5 years ago – whenRAM memory was still expensive, whenbringing home a 1 Ghz computer waspossible only for rich students, and whenhigh-speed Internet access was only adream. If there is a class of people thatknows how to use computers and browsethe Internet, it is undoubtedly collegestudents. The future of academia lies

within the Internet. The possibilities areendless: simulations, virtual rooms withvirtual three-dimensional reconstruc-tions, pages and pages of illustrations,and almost infinite cross-hyperlinksbetween different sources. We are surethat publishers have the same vision ofgathering academic data in places whereeveryone, regardless of geographicsituation, can visit and use it at leisure.

Indeed, Principles of Developmentcanbe visited at the Oxford University Presswebsite, where some of the text and allof the book’s pictures have been madeavailable to the public. We welcome thisinitiative as well as Lewis Wolpert’seffort in bringing this unique updatedversion of the core of development to thebiology classroom.

All at the tip of a needleNadia Rosenthal

EMBL Mouse Biology Programme, Monterotondo, Italye-mail: [email protected]

Development 130, 5566© 2003 The Company of Biologists Ltddoi:10.1242/dev.00862

Manipulating the MouseEmbryo: A LaboratoryManual, 3rd EditionBy Andras Nagy, MarinaGertsenstein, Kristina Vintersten andRichard BehringerCold Spring Harbor Laboratory Press (2003)764 pagesISBN 0-87969-591-9£85.00/$115.00 (paperback)

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5567Book reviews

visualizing gene products, cells, tissuesand organ systems. On the molecularside, the section on vector design(Chapter 9) presents the latestconditional and inducible gene stra-tegies, the ins and outs of BAC and YACcloning, and novel reporters. Although Ifound the icons used to denote the DNAmanipulations too small and hard tofollow, an exhaustive array of geneexpression tips and pitfalls makes thissection a definitive resource andteaching tool. There’s even a companionwebsite with supplier links andinformation, Medline-linked references,and links to other databases of value toscientists working in this field, whichhas the advantage that supplementaryinformation can be added after the bookis published.

Reorganization of the book wasnecessary, given the amount of newcontent, and has made this third editionmore practical. Easy-to-find referenceshave been collated at the end of eachchapter. A glossary of the mousegenome in the second edition was ratherinadequate and has been omitted – it’s afield in itself by now – and surgicaltechniques have been grouped togetherin one very helpful chapter. However,there are some confusing aspects to thenew order. Whereas the misleadinglynamed Chapter 3 (Production ofTransgenic and Chimeric Mice: GeneralIssues) is primarily about establishingtransgenic mouse colonies, Chapter 7(Production of Transgenic Mice) is moretechnical, with important molecularinformation and detailed protocols. Inall fairness to the authors, such acomplex package makes it hard to knowwhich should come first, the chicken(sic) or the egg.

There are some practical additions, suchas a detailed ‘how to...’ section onsetting up your own micromanipulationlab that will be of great value toscientists just starting out, and toestablished research groups switching tothe mouse model. There is also acautionary appendix that expounds thedangers of hazardous materials used inthe protocols. Of particular relevance inthis time of exploding mouse colonysizes, escalating animal costs and

limiting housing space, when gettingmice off the shelf is becoming anincreasingly pressing priority, is thesection on embryo and gametecryopreservation and re-derivation.There is even an informative discussionof mouse colony trends (we’ve come along way since 1986!).

The book looks classier too. Many of thecartoons, including fate maps of earlymouse embryogenesis by theincomparable artist/scientist RosaBeddington (an original author of thismanual, see Fig. 1) have been retained;however, other diagrams have beenredrawn to illustrate the techniques moreclearly. New colour photographs showreal-life results of current geneticstrategies. Alas, the old ring-bookformat is gone, presumably a casualty ofthe volume’s increased girth, but thesturdy spine of the current paper editionwill hopefully stand up to the constantthumbing and flattening on the lab benchthat have dog-eared my two previouseditions.

So what’s wrong with this edition? Notmuch. But well, let’s see, there’s noheart development in the embryologysection. This subject mysteriouslydidn’t rate in the second edition either.Call me biased (alright, I admit I workon heart development), but the lateralmesoderm gives rise to more than thekidneys. The heart is the first organ toform and function in mammaliandevelopment, and its prominent andeasily visible position during mouseembryogenesis makes it a very helpfulsignpost.

I would have also liked to see acompendium of protocols listedsomewhere in the book, and a bit morecross-referencing would have beenuseful. For example, Protocol 1 on p.435 (Electroporating DNA into ES cellsand selection methods) is related insubject matter to Protocol 1 on p. 469(Preparation of ES cells for injection).While we are on the subject of cross-referencing, the index is regrettablyuneven. I will forgive the absenceof cardiovascular terms (the wordsheart, cardiogenesis, circulation andvasculogenesis, didn’t even make it intothe index, and I checked, heart-brokenly). Omission of the term ‘geneknockout’, on the other hand, is a moreserious oversight, particularly as none ofthe chapter headings lead the uninitiatedreader to the appropriate pages(knockouts are discussed in Chapter 9,‘Vector design for ES cell-basedtransgenesis and genomic alterations’,for those of you who were wondering).

In the greater scheme of things these aretrifling concerns, especially consideringthe breadth of scope and depth ofcoverage the authors have achieved. Iagree with the Cold Spring HarborLaboratory Press promotional blurb thatthis book is the “premier authoritativeand comprehensive source of technicaland theoretical guidance for mousedevelopmental biologists and geneti-cists”. It is helpful whether you aretempted to start your own mouse facility,or merely interested in making a singletransgenic or knockout animal. Itincludes a marvelous summary of ourcurrent understanding of mousedevelopment, and offers students andteachers alike an updated approach tomammalian genetic manipulation. It isbrimming with useful and excitinginformation for the adventurous postdocwho is ready to embark on the generationof a conditional mutation, and it is a one-stop shop for the seasoned developmentalgeneticist looking for the latest tricks ofthe trade. But the best thing about thisbook is the sense of exuberance that theseauthors convey about their subject. Youcan feel their enthusiasm radiating up atyou as you read. It is a tremendous timeto be a mouse biologist. I am still asexcited as I was in 1986.

Fig. 1. Sketch by Rosa Beddington.Courtesy of NIMR (London, UK).