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‘There is an intangible something aboutthe process of gastrulation thatinvariably generates enormous awe andcuriosity’, writes Claudio Stern in thePreface to an excellent and timely bookthat he has edited, titled Gastrulation:From Cells to Embryo, and that has beenrecently published by Cold SpringHarbor Laboratory Press. Indeed, it isthe process of gastrulation thattransforms an unimpressive, amorphousheap of cells that makes up each animalat the blastula stage of development, intoa gastrula in which three germ layers,the endoderm, mesoderm and ectoderm,are shaped into a body plan that ischaracteristic of each systematic group.It is also during gastrulation that largelypluripotent embryonic cells becomeinitially biased, then specified andfinally committed to form specializedcell types such as muscles, blood andneurons. Thus, a two-dimensional mapof tissues and organs in the blastula istranslated through dramatic gastrulationmovements into a three-dimensionalconfiguration. In this triploblasticstructure, the future skin and neuraltissues reside in the most superficialectoderm, the prospective alimentarystructures form from the most internalendoderm layer, and sandwichedbetween these two is the mesodermallayer, which will give rise to thecardiovascular organs, musculature andbones.

Gastrulation is accomplished by theconcurrent and concerted actions of fourevolutionarily conserved morphogeneticmovements. Epibolic movements resultin the expansion and thinning of tissues;internalization movements (emboly)bring future mesodermal andendodermal germ layers beneath theectoderm; and, lastly, the nascent germlayers narrow mediolaterally throughconvergence movements, whileextension movements elongate themfrom head to tail. This dynamic andcomplex combination of cell

movements, rearrangements andinductive events during gastrulation is sointriguing, almost magical, that manystudents, upon encountering it, becomehooked forever.

The same features of gastrulation thatmake it an object of fascination also makeit a challenging subject of study. Whereasin the past two decades embryologists,geneticists and molecular biologists

made large strides in our understandingof the inductive processes that specifyembryonic polarity, germ layers and theirpatterning, the morphogenetic aspects ofgastrulation proved to be less tractable.Consequently, only a few books thatfocus on gastrulation have beenpublished in recent decades (Keller et al.,1991; Stern and Ingham, 1992).

In recent years, however, new imagingand cell tracing technologies,

fluorescent fusion proteins, as well asnew molecular and genetic approachesin many model systems, have begun tounveil the mysteries of gastrulation.Many molecular pathways have beenimplicated in this process, and in somecases have been linked to individualgastrulation movements, or even tospecific cell behaviors. This fast rate ofdiscovery in gastrulation research islikely to continue. Although severalreviews have been published that focuson individual model systems, or on theroles of specific pathways ingastrulation, a comprehensive andcurrent view of gastrulation has beenmissing. For the gastrulation enthusiast,hungry for a good and modern source ofinformation, the new book edited byClaudio Stern is simply a feast. It is themost extensive treatment of gastrulationyet attempted in book form. The editorhas collected together an impressiveconstellation of experts in the field towrite for the book, who havecontributed 54 chapters discussingindividual aspects of gastrulation. It iscarefully crafted with the first chapterplacing the study of gastrulation into ahistorical context. A short glossary atthe beginning of the book will also helpuninitiated readers to appreciate theintricacies of gastrulation. Chapters arewritten in an accessible style andinclude effective illustrations.

Gastrulation is a truly organismalphenomenon, whereby the entireembryo changes its architecture andshape through the concerted movementsof individual cells, cell populations andcellular sheets. These morphogeneticcell behaviors are precisely regulated intime and space, and are coordinated withcell fate specification events. Thespecification of both cell movementbehavior and fate likely reflect thecurrent position of a cell in the embryo,as well as its developmental history.Therefore, the complete set ofinstructions on how to construct an

Unfolding gastrulationLilianna Solnica-Krezel

Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USAe-mail: [email protected]

Development 131, 5767-5769Published by The Company of Biologists 2004doi:10.1242/dev.01518

Book reviews

Gastrulation: From Cells toEmbryoEdited by Claudio D. SternCold Spring Harbor Laboratory Press (2004)731 pagesISBN 0-87969-707-5$150.00 (hardback)

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embryo during gastrulation from itscellular constituents must be encoded inthe genome. The book takes thisreductionistic approach to gastrulation,guiding the reader from the embryonicthrough cellular level, and finally to themolecular genetic mechanisms ofgastrulation. In the first part, ‘TheEmbryology of Gastrulation’, we learnabout gastrulation movements indifferent animals, from simple spongesto humans. A real strength of this bookis that it is not limited to the mostpopular model systems; it also featureschapters that describe gastrulationmovements in less well-studiedorganisms, such as crustaceans,ctenophores, mollusks, dogfish, reptilesand the rabbit. On the one hand, thesechapters illustrate the wonderfuldiversity of gastrulation movementsamong metazoans, and on the other, theyreveal that the basic types ofmorphogenetic movements of epiboly,internalization, convergence andextension are universally, albeitsomewhat differently, employed bythese distinct organisms.

Getting down to the cellular level, PartII considers the morphogenetic cellbehaviors that execute gastrulation,including how they are patterned in timeand space. The reader will enjoyexploring various mechanisms ofmesendoderm internalization, such asinvagination, involution and ingression,or their intermediates such as‘synchronized ingression’, which isproposed to occur in teleost gastrulae.Gastrulation aficionados will appreciatedelving into more complex issues. Forexample, how local morphogenetic cellbehaviors, such as intercalations thatare uniform across a cellular field,might result in different rates ofmovement in distinct regions of thefield. A few chapters consider the roleof chemotaxis and the extracellularmatrix in orchestrating gastrulation cellbehaviors. In this part of the book, onecan also learn about the inductive andpatterning processes through whichembryos gear up for the morphogeneticmovements of gastrulation. After all,gastrulation movements makeembryonic asymmetries morpho-logically apparent, but theseasymmetries are established before themorphogenetic movements are

initiated. Several chapters provideoverviews of the early symmetrybreaking events in distinct embryos,such as frog and mammals. The nextseries of chapters guide the readerthrough processes that specify and thenpattern the mesodermal, endodermaland ectodermal germ layers. Theconcepts of morphogens and theirspecific deployment in patterning thenascent mesodermal and neuro-ectodermal tissues are discussed. Iespecially enjoyed reading thesechapters, as they do not focus on anyparticular animal model, but rather takea comparative approach. Of note hereare the chapters discussing endodermdevelopment and the specification of theleft/right axis, two areas that haveexperienced particularly fast progress inrecent years.

But it is Part III, concerning ‘TheMolecular Biology of Gastrulation’,that makes this book qualitativelydifferent from its predecessorspublished a decade ago. Whereas onlya handful of pathways and moleculeswere linked to inductive ormorphogenetic events of gastrulationat that time, now almost 20 chapters ofthis book are devoted to either thedifferent signaling pathways (all theusual suspects from Nodal, throughFGFs and the canonical and non-canonical WNTs, to BMPs andNotch), the array of transcriptionfactors, or the extracellular matrixcomponents involved in gastrulation.This part of the book illustrates therapid progress in our understanding ofgastrulation, but it also articulatesmany outstanding questions and futureexperimental priorities. For example,we learn that among the genesimplicated in gastrulation, those thatimpact primarily on embryonic patternand cell fates predominate overthose regulating only morphogeneticcellular behaviors. Therefore, thequestion remains as to the relationshipbetween genes regulating cellular fatesand those regulating movementsduring gastrulation. However, fewanswers can be offered at the moment.Another conclusion emerging fromthis part of the book is that withincreasing knowledge of the molecularplayers in gastrulation comessomewhat daunting complexity. It

becomes clear that a gastrulating cellneeds to integrate its positionalinformation, developmental historyand a multitude of movement cuesfrom several sources. The chapter‘System-level Properties Revealed bya Gene Regulatory Network Analysisof Pre-gastrular Specification in SeaUrchins’ offers a view of how suchcomplex molecular information can beharnessed.

Part IV looks at gastrulation from theevolutionary perspective, exploringfossil embryos, as well as taking acomparative approach to cellular andmolecular aspects of gastrulation inmodern animals. Chapters in this part ofthe book illustrate well the symbioticrelationship between the studies ofevolution and gastrulation; we learnabout the evolution of animals bystudying their development and viceversa. The final chapter of the book iscontributed by Lewis Wolpert, a long-standing proponent of the importance ofgastrulation over the less exciting eventsin life such as birth, death or evenmarriage. He considers the progressachieved in the field, as well as thechallenges ahead, concluding that manyof the mysteries of gastrulation are stillto be uncovered.

The limitations of the book are few andlargely unavoidable. The rate ofprogress in the area of gastrulationresearch is so rapid that, even in a bookstill hot off the press, important newregulators of gastrulation such as STAT3and its downstream effector LIV1 arenot discussed. Whereas there was aneffort to maintain a uniform colorscheme for germ layers and specifictissues in the book’s illustrations, thiscould be more consistent. Moreover,some colors must have been misprintedduring the printing process, with yellowlooking rather greenish in somechapters. These are, however, onlyminor issues in this otherwiseoutstanding book.

Gastrulation is a dynamic process andnothing illustrates it so well as movies.The book is associated with amodest but useful web site(www.gastrulation.org) where time-lapse movies of live embryos, orschematic visualizations provide an

5769Book reviews

excellent addition to the individualchapters. This website will likely growwith new editions of the book, orpossibly take on a life of its own, withnew materials being added as theybecome available.

In conclusion, I enthusiasticallyrecommend this book, and expect it

will be highly valuable to students,teachers and researchers. Thebook provides a comprehensive,authoritative and modern view of ourknowledge of gastrulation, andcaptures the excitement in this rapidlydeveloping field. I imagine that manyyoung readers will become intrigued bygastrulation and at least a few will

become hooked by it forever afterreading this book.

ReferencesKeller, R., Clark, W. H., Jr and Griffin, F.(1991). Gastrulation. Movements, Patterns, andMolecules. New York and London: Plenum Press.Stern, C. D. and Ingham, P. W. (eds) (1992).Gastrulation (Development supplement).Cambridge, UK: The Company of Biologists.

What is the main driving force ofevolution? What determines thedirection of evolutionary change? Whatcauses novelties to arise? During most ofthe last century, these questions havebeen addressed by evolutionarybiologists and the answer they havecome up with is well known, not only tobiologists: it’s natural selection. In hislatest book, Wallace Arthur forces us tore-think. He claims that besides naturalselection, there is embryologicaldevelopment as a second major playerdetermining the direction of evolutionarychange.

Biased Embryos and Evolution is a shortbook, which is easy to read and aimedat both biologists and general readers.Although laid out in 17 chapters, it hasa straightforward, if provocative,message: ‘natural selection is not themain orienting agent of evolution, asDarwin claimed. Rather, it is one partnerin an interacting duo’. Arthur claims thatdevelopmental bias, ‘the tendency of thedevelopmental system of a creature toproduce variant trajectories in somedirections more readily than others, is asecond major agent of evolution’. Hestarts his argument by summarizingtextbook thinking in developmentalbiology, evolutionary biology and thehistory of life. But already in the firstpart of the book, he sets the stage for hisprovocative statement by highlightingthe limitations of the modern synthesis.Arthur argues that the contributions ofFisher, Haldane, Wright, Dobzhansky,

Mayr, Ford and Simpson were allcorrect and important, but what followedwas often an ‘arrogance about thesynthesis that was entirely absent fromDarwin’s beautiful book’. Theimportance of mutations that affect thedevelopment and, ultimately, themorphology of an organism has beenlargely ignored in the modern synthesis.Therefore, it is more than logical thatone of the central chapters of Arthur’sbook is entitled ‘The Return of theOrganism’. What follows is an excellentaccount of how development influencesevolution and how developmentalbiology can influence evolutionarytheory.

Evolutionary change has three majorcomponents: mutation, which acts at thelevel of the gene; natural selection, whichacts at the level of the population; anddevelopmental reprogramming, whichacts at the level of the organism. Arthuruses ‘developmental reprogramming’ asan umbrella term to describe the manyways in which mutations can affect thetiming (heterochrony), the spacing(heterotopy), the quantity (heterometry)or the quality (heterotypy) ofdevelopmental processes. It is at thispoint, at the latest, that it becomes clearthat when Arthur talks about the‘organism’, he mostly means thedevelopment of the individual. Molecularchanges brought about by mutationsaffect developmental processes, causedevelopmental reprogramming, andthereby generate developmental and

morphological novelty. Although we arefar from having a full account ofdevelopmental reprogramming between,and within, any major groups of animalsor plants, there are many case studies ontheir way that will ultimately providefresh data to support this theoreticalassumption. At the same time, the scarcedata already available clearly support the

Beyond Darwin – towards an inclusive evolutionary synthesisRalf J. Sommer

Max Planck Institute for Developmental Biology, Department for Evolutionary Biology, Spemannstrasse 37, 72076 Tübingen,Germanye-mail: [email protected]


Biased Embryos andEvolutionBy Wallace ArthurCambridge University Press (2004) 248 pagesISBN 0-521-54161-1 (paperback)ISBN 0-521-83382-5 (hardback)£18.95 (paperback)/£50.00 (hardback)


importance of incorporating develop-mental thinking into evolutionary theory.

And here it comes: the book is neitherunique nor novel in its attempt topostulate a closer interdependencebetween evolution and development –this theory is already at the heart ofevolutionary developmental biologyand several books and even morereviews have been written on this topic.What is novel, and what is onlysuperficially discussed in the lastparagraphs of original evo-devoresearch papers, is the way in whichdevelopment can influence the directionof evolutionary change. This is whatArthur calls ‘developmental bias’, andwhat Gould, Lewontin and others havetermed ‘developmental constraints’ informer times. Arthur makes asignificant contribution to this debate byclaiming that one of the reasons for thelimited acceptance of the term‘developmental constraint’ is itsnegative touch. He argues that‘development biases evolutionarydirections in both positive (drive) andnegative (constraint) ways’. Thus, theinternal factors in evolution, thegenome and the developmental programon which mutations act, can have a

positive or a negative effect. They makesome changes more likely than others,and thereby are important componentsin the evolutionary game. There is nodoubt that these considerations and thegrowing knowledge in the field of evo-devo have to be incorporated in an‘inclusive’ evolutionary synthesis.

‘So what?’, the evo-devo folks will ask.We all agree on this, and many of usexpress it one way or the other in ourpapers. However, even if this thinking iscommon, original research papers neverprovide the space for developing thisidea all the way through. Wallace Arthurhas taken the time and energy to write abook to precisely drive home that point.In order to do that, he had to criticize‘neo-Darwinian’ thinking, which he didin a balanced way, while still gettingacross the important point of the‘incompleteness’ of the modernsynthesis. Even if some people mightnot like this style, I believe he deservescredit for doing it the way he did. Thebook is therefore not just anotheraddition to the long list of monographicevo-devo texts. Arthur has a novel andimportant point. His argument is shortand precise. He does his readers, butmostly himself, the favor of driving this

point home straight. The style of thebook is entertaining and light-hearted,and includes some gossip, which makesit even more rewarding for the non-specialist.

In conclusion, I highly recommendArthur’s book to all fellows ofdevelopmental and evolutionarybiology. Not that they will learn from itnew details in evo-devo, that is not theaim of the book, and Arthur was well-advised in not even trying to persuadethe reader with case studies in order tomake his argument. Rather, he urges us(in particular the evolutionarybiologists) to be open-minded and toaccept the concept of ‘developmentalbias’ as a major addition to theevolutionary synthesis. The time wasripe for a distinguished fellow – such asWallace Arthur – to make the claim thatembryological development can make aspecific contribution to evolutionarytheory, and that without it the ‘modern’synthesis cannot be complete. If thebook can persuade evolutionarybiologists to embrace its centralmessage as whole-heartedly as the evo-devo crowd surely will, it will haveserved its purpose. Hopefully they’llread and re-think.

The editors of this compilation declaretwo goals: to show how computerscience can help us to understandbiological development, and to showhow ideas from developmental biologycan stimulate new thinking in computerscience. The objectives are neatlysymmetrical, but they do not sitcomfortably together. Developmentalbiologists and computer scientists speakdifferent languages and inhabit differentworlds. On one side of the culturaldivide, the developmental biologistsstruggle to digest complex experimentalfindings and make sense of them,tangled in wearisome quantities of datathat defy quantitative analysis. On the

other side, the computer modellersconstruct ingenious idealized systems,with a blithe disregard for biologicalrealities and a greater concern for whatis possible than for what is actual. Aterrible jungle or a ridiculous toyland: inbad moments that seems to be thedichotomy. The question in my mind asI embarked on On Growth, Form andComputers was whether it would showus some happy middle ground, wherecomputer modelling casts clear freshlight on the workings of biologicalsystems, and in particular of realdeveloping organisms.

The book begins with an introductory

chapter that is mainly addressed tocomputer scientists and in which, amongother things, the editors rashly undertaketo summarise developmental, cell andmolecular biology in nine pages for thebenefit of those who do not know aboutthese things. The rest of the bookconsists of 21 heterogeneous essays bydifferent authors, including six piecesthat are reprinted from otherpublications. The first few contributions(Wolpert on development and evolution,Hancock on cell signalling, Bolker onthe genotype-phenotype relationship,and Brockes and Kumar on amphibianregeneration) discuss aspects ofdevelopmental biology but say little or

Between toyland and the jungleJulian Lewis

Vertebrate Development Laboratory, Cancer Research UK, London, UKe-mail: [email protected]


5771Book reviews

nothing directly about computermodelling. Developmental biologistswill find some things to interest themhere, but not much enlightenment on themain theme of the book.

Subsequent chapters get down to brasstacks, and fall roughly into two groups.First come those directed towardsbiological questions – attempts to usecomputer modelling to understandspecific developmental systems, as wellas general essays on the application ofmathematics or computer modelling todevelopmental biology. Second, thereare accounts of computer constructsinspired by ideas from biology, butstudied by computer scientists for theirown sake. A good representative ofthe first category is Meinhardt’scontribution, reviewing the work forwhich he is famous on the role of short-range activation and long-rangeinhibition in the creation of spatialpatterns of differentiation. Even thoughit has been difficult in most cases tosubstantiate Meinhardt’s models withdetailed quantitative data, and some ofMeinhardt’s specific applications arehighly speculative, his basic ideas abouthow symmetry is broken and signallingcentres are set up are simple andilluminating, and are backed up byserious consideration of specificbiological examples. They have becomea significant part of the developmentalbiologist’s conceptual toolkit, helpingus to think about how real systemswork. The breaking of symmetry iscertainly fundamental to patternformation, and this is emphasized in anice (reprinted) essay on the subject byIan Stewart, although his finaldisquisition on the symmetryclassification of the gaits of quadrupedsstrays rather far from the theme of thisbook.

The book contains relatively fewcontributions that focus on oneparticular developmental system andshow how computer modelling canreally help us understand it. This is apity, and perhaps a reflection of theeditors’ backgound as computerscientists rather than developmentalbiologists. The book does, however,include an essay on one of the mostinteresting systems from this point ofview, the shoot apical meristem, with its

regular sequential emergence of leafprimordia, each one positioned preciselyin relation to those already present.Work in the last few years has identifiedmany of the key molecules governingthis process, to the point where a closeinteraction between experimentalistsand modellers can be very fruitful. Thechapter by Jönsson, Shapiro,Meyerowitz and Mjolsness describesone such collaboration, although it is toobrief and condensed to do the subjectjustice.

A central task for computer modellers,addressed by several contributors (e.g.De Jong, Geiselmann and Thieffry, andReil), is to describe and analyse thebehaviour of gene regulatory networks.The standard approach is throughpartial differential equations. Thedifficulty is that in most biologicalsystems we have only an incompleteknowledge of network topology, and,worse still, virtually no informationabout the quantitative parameters ofthe regulatory mechanisms: theexperiments may tell us that X goes upwhen Y goes down, but they rarely tellus how steeply, or within what range ofconcentrations, or with what sort ofnon-linearity. One response is to is tomake models that avoid quantitative

description and seek to represent theavailable qualitative information interms of logical (yes-no) variablesinstead of continuous variables. Thefallacy is that such idealizations, at leastfor networks with feedback, sadly fail tocapture correctly even the qualitativebehaviour of the underlying continuumsystem. Even if we only want to makequalitative predictions, we have to havequantitative information. The lack ofquantitation is, I think, the fundamentalreason why developmental biology hasyet to find its Newton, or its Hodgkinand Huxley.

These problems become more severe,and the computer models markedlymore complex and difficult to construct,when cell movement and cellrearrangements also have to be takeninto account. Several chapters (e.g.Miodownik, Fleischer, EggenbergerHotz) discuss this enterprise and conveya flavour of the problem, though with anemphasis on general principles andidealized systems, rather than onanalysis of specific real cases.

A still more ambitious undertaking is tomodel the evolution of developmentalprograms. This involves setting up adescription of the rules of generegulation, cell proliferation and cellmovement, computing the resultantphenotype, and then allowing the rulesto change through successive rounds ofmutation and reproduction, withselection applied according to somemeasure of fitness of the computedphenotype. Hogeweg’s studies of her‘critters’ are an example. Here, as inmost undertakings of this sort, theassumptions needed to construct atractable model become so artificialthat it is hard to identify anycorrespondence with a specific realbiological system. Whether usefulinsights are gained into generalbiological principles is a matter ofdebate.

The chapters in the final section of thebook for the most part abandon anyclaim to answer specific concretebiological problems. They ask notwhat computer science can do forbiology, but what biology can do forcomputer science. They are addressedprimarily to computer scientists, and

On Growth, Form andComputersEdited by Sanjeev Kumar and PeterJ. BentleyAcademic Press (2003) 444 pagesISBN 0-12-428765-4£69.95 (hardback)

This is a beautifully writtenphilosophical book on the nature of thedevelopmental process, and on bothpast and current thinking about itsrelationship with evolution. I wouldurge all developmental andevolutionary biologists to read it. Youwill probably find, as I did, that thereare some things you agree with andsome that you don’t. But of course,’twas ever thus.

I’ll start with the things that I liked.Jason Scott Robert is enthusiastic aboutthe new ‘evo-devo’ approach, andhe emphasizes its philosophicalsignificance, rather than its minutiae. Inparticular, he notes the possibility thatdevelopment may ‘bias’ (p. 32) or‘drive’ (pp. 101-102) evolution inparticular directions – something that Ihave long felt to be important (Arthur,2004). However, he also draws attentionto ‘developmental systems theory’(DST), the existence of which hadentirely escaped me, as it seems to havebeen a story told largely in thephilosophical, rather than the biological,literature (not that this is any excuse for

my having missed it). In particular,Robert focuses on the work of Oyama[(Oyama, 1985) and subsequentpublications]. The main differencebetween DST and evo-devo, accordingto Robert, is that the former adopts aholistic stance in which genes are simplysome of the players in a verymultifactorial process, whereas muchevo-devo is centred on comparisons ofgene expression patterns betweendifferent taxa, and so tends to emphasizethe roles of genes above those of theother players in the developmentalgame. I’m sure there’s some truth in thiscontrast, although my own view of evo-devo is that it is also a holisticendeavour. But in any event, Ientirely agree with one of Robert’sclosing comments – that ‘evolutionarydevelopmental biologists and develop-mental systems theorists would do wellto interact with each other inestablishing a genuinely syntheticbiology’ (p. 130).

And so to the location of the Devil.Robert’s final chapter is entitled ‘TheDevil is in the Gestalt’. By this, he

means that it is in the flavour of thewhole, and not in the detail, where theDevil is proverbially to be found. Theparticular devil to which Robert isalluding is that of actual, or apparent,disagreement between different campson the nature of the relationshipbetween development and evolution.And I believe that he’s right in hisidentification of its location. Few if anyevo-devo folk would deny theimportance of population processes,such as changing gene frequencies, inevolution (though of course they dorebel against the excesses of some neo-Darwinians, such as those who defineevolution as changes in genefrequency). Equally, few, if any, of themore enlightened wing of neo-Darwinism (such as quantitativegeneticists) would now deny thepossibility that development mayindeed often ‘drive’ or ‘bias’ evolutionin certain directions. But the emphasesof the two endeavours are still muchmore different than they should be. Ithink this is a case of the need todiscard historical baggage, and I


make rather hard, though interesting,reading for outsiders. So far, the mainachievement of biologically inspiredcomputing has been to cause everyonea lot of trouble, in the form ofcomputer viruses. The book passesover these in silence; the emphasisinstead is on more benign forms of‘artificial life’ – that is, on non-malignant computer programs thatevolve by random mutation andselection according to the output thatthey produce. Ray and Hart (in areprinted paper) do, however, explorethe evolution of software constructsthat can migrate from computer tocomputer to computer, sense theirenvironment, and compete with oneanother. ‘Artificial life’ is a rich and

intriguing topic, with practicalapplications to such things as thedevelopment of control systems forrobots (discussed by Jakobi). It raisesmany general questions. Will suchcomputer constructs tend to evolve inthe direction of increasing size andcomplexity? If the selected phenotypeis behavioural, reflecting theconnectivity of a control network, howwill the structure and performance ofthat network evolve (Rust, Adams,Schilstra and Bolouri; Dellaert andBeer)? What course will evolution takeif the programs operate in a variableenvironment and are capable of‘learning’ from ‘experiences’(discussed by Cangelosii, Nolfi andParisi)? Will the programs evolve to

outstrip the ingenuity of their humancreators? The last few chapters of thebook do not give straightforwardanswers to questions such as these –none, at least, that I as an outsider tothe field could easily grasp; but theyprovide much food for thought.

In short, the book is a mixed bag.Reading it makes one all too well awareof the difficulties of the relationshipbetween developmental biology andcomputer modelling. There are somenicely written essays that make goodpoints of principle, but few shiningexamples of models that succeed inadding to our understanding of specificevents in the development of realorganisms.

Searching for the DevilWallace Arthur

Department of Zoology, National University of Ireland, Galway, Irelande-mail: [email protected]


5773Book reviews

believe that Robert’s book will help toachieve this.

Finally (in terms of my likes), the bookis not only well written but also wellstructured, with ‘summaries of theargument so far’ available at sensibleplaces, just when you feel the need forthem. It also has a certain humility ofstyle that is endearing. At one point(p. 90), Robert goes so far as tocontemplate the possibility that his bookmight be considered to be ‘verbalgymnastics’ that are ‘utterly useless topracticing biologists’. Of course, hedoesn’t really believe this is true, andneither do I. It is entirely sensible, evenperhaps necessary, for practisingbiologists to stand back from theindividual trees from time to time, andto reconsider the nature of the wood.

Now for the things I didn’t like. Thereare just two of these, but they’re bothimportant, one from a scientific and onefrom a historical perspective. I’ll discussthem in that order.

In his favouring of a holistic stance,Robert sometimes goes too far. In tryingto correct what he sees as an overplayingof the role of genes, he sometimes

comes across as not being balanced butrather as being equally unbalanced – inthe opposite direction – as the folk hecriticizes as being too pro-gene. So, hesometimes seems almost anti-gene, and,associated with this, anti-geneticprogramme For example, he states that‘we don’t need genetic programmes orinstructions, or even specifically geneticinformation, in order to understand andexplain the developmental effects orevolutionary significance of genes’(p. 31).

Now this is one of the craziest statementsin a generally sane book, and I suspect itis one that the author himself, inretrospect, might feel slightly uneasyabout. But his dislike for geneticprogrammes re-surfaces all over theplace, usually in less extreme forms. Forexample, in the context of a reference tothe work of Keller [(Keller, 2001) andothers], he states (p. 86) that ‘the genomedoes not itself contain or comprise aprogramme for development’. I havemixed feelings about this. If he simplymeans that epigenetic and environmentalfactors also influence the course ofdevelopment, then I (and probablyeveryone) would agree. However, I havetended to think of development as aninterplay between a genetic programmeand an epigenetic programme, with thatinterplay itself being potentially alteredby many environmental variables(Arthur, 2004). So in my view, the ideaof a genetic programme, if used broadly,is entirely compatible, rather than atodds, with a holistic view ofdevelopment. This train of thought leadsinexorably to a crucial question: exactlywhat is meant by a ‘programme’? I washoping that Robert would devote asubstantial block of text to this issue (inthe same way that he does for themeaning of modularity on pp. 122-124),but I was disappointed to find that he didnot.

Now to my historical gripe, whichconcerns our current interpretation ofthe work of Haeckel. Robert re-iteratesthe view of some other recent authorsthat ‘according to Haeckel, theancestral stages of adults could beidentified in the embryos ofdescendants’ (p. 94). He refers to Hall(Hall, 1999) here rather than to any ofHaeckel’s works. Personally, I don’t

buy this argument. Although Haeckelmay have thought that ‘higher’vertebrate embryos pass through, forexample, a ‘molluscan’ stage, did hereally think that they resemble adultmolluscs? If so, which ones? Perhaps agarden snail or an octopus? Surely not.It is clear from some of Haeckel’s laterwork that he did not think in this wayat that stage of his life. I will only bepersuaded that he thought in this way atan earlier stage if someone can come upwith a specific quotation to that effect.Meanwhile, anyone interested in thisissue should consult Sander (Sander,2002).

In conclusion, I liked more than Idisliked Robert’s book. And I think itsmain virtue is to force readers to reflecton where theoretical biology in general,and evo-devo in particular, are going,both philosophically and scientifically.Such reflection is all the more necessaryin these pressured times, when manybiologists feel forced to concentrate onthe latest-emerging details in their ownparticular neck of the woods, in order tokeep sufficiently up to date to get thatnext grant. Of course, without researchfunds, few of the details that ultimatelyaccumulate to give us somethingsubstantial enough on which to reflectwould be discovered. So, like much inlife, it is all a question of balance.Despite some ups and downs along theway, on reaching the final page I felt thatI had become better balanced than I hadbeen before beginning this interestingbook.

ReferencesArthur, W. (2004). Biased Embryos andEvolution. Cambridge, UK: Cambridge UniversityPress.Hall, B. K. (1999). Evolutionary DevelopmentalBiology, 2nd edition. Dordrecht, Germany:Kluwer.Keller, E. F. (2001). Beyond the gene but beneaththe skin. In Cycles of Contingency: DevelopmentalSystems and Evolution (ed. S. Oyama, P. E.Griffiths and R. Gray), pp. 299-312. Cambridge,MA: MIT Press.Oyama, S. (1985). The Ontogeny of Information:Developmental Systems and Evolution.Cambridge, UK: Cambridge University Press.Sander, K. (2002). Ernst Haeckel’s ontogeneticrecapitulation: irritation and incentive from 1866to our time. Ann. Anat. 184, 523-533.

Embryology, Epigenesis, andEvolution: TakingDevelopment SeriouslyBy Jason Scott Robert Cambridge University Press (2004) 158 pagesISBN 0-521-82467-2 £40.00/$60.00 (hardback)


In its broadest sense, polarity can bedescribed as asymmetry. And, if youlook at a plant, you will immediatelynotice a variety of asymmetric featuresat different levels of complexity. Thereis a root at the bottom and a shoot at thetop. Leaves are attached to the shoot atone end and are free at the other. Theupper side of the leaf may have hairs onit, while the underside is smooth. Whenyou take a closer look at a hair, youmight see that it is asymmetricallybranched. If you happen to have amicroscope handy, a cross-section of theplant’s stem will reveal that the cells atthe core look different from thosefurther out. Even better equipped, youwill recognize polarity at the cellularlevel, which manifests itself in thedirections of vesicle movement and inthe asymmetric distribution oforganelles, cytoskeletal strands, andeven of single proteins. Finally, if youare really inquisitive and do not mindleaving the realm of biology, you can gofurther and look at the polarity of singlemolecules, atoms and elementaryparticles, and end up in the dark and vastspace of the ultimate microcosmos (butplease be back for lunch). You have justdiscovered different levels of polarity atdifferent orders of magnitude, nestedlike Russian Matryoshka dolls, and youmay speculate that polarities at lowerlevels in some way underlie the polarityfound in bigger structures.

In general, polarity is a very commonphenomenon and it is an intrinsicproperty of matter at every level ofcomplexity. However, for plants, polarityis something more – it is the means bywhich they maintain developmentalcontinuity, communicate, expand andadapt. For plants, polarity is a real themeof life. In his new book Polarity in Plants,Keith Lindsey explores the multiplelevels at which polarity arises and theintegral role that polarity plays duringdevelopment. In spite of the obviouspresence of polarity in plants and the

attention that has been given to this topicfor centuries, we are only beginning tounravel the complex mechanisms thatunderlie cellular polarity and itsconnection to the polarity of tissues,organs and the whole plant. The plantpolarity field is still in its infancy;delimitation of the field is unclear, manyconcepts are intriguing but largelyspeculative (such as the analogies drawnbetween auxin and neurotransmitters),and there is a lack of consensus aboutbasic nomenclature (for example, theissue of whether the tip of the root shouldbe referred to as an apical or a basalstructure). Above all, polarity exists atmany different structural levels, and theseissues make plant polarity a very difficulttopic to discuss in a comprehensivesynopsis, as it does not break down easilyinto small, separate entities that can bepresented in an intuitive sequence.

Keith Lindsey has arranged the elevenreviews about various facets of polarityin plants that make up this book in alogical way, along the axes of both spaceand time. The first few chapters, whichhave been written by variouscontributors, cover polarity at the single-cell level, with special considerationgiven to the cytoskeleton and cell walls.The rest of the book follows the courseof plant development. It starts withpolarity in the zygote and duringembryogenesis, and then considers thedifferent organs and tissue structures asthey develop in time, which eventuallyleads us to the ‘abominable mystery’ ofpolarity in flowers. This structureprovides for a book that is relatively wellrounded, in spite of the variable scopeand style of the single reviews.

By and large, the chapters are ‘standalone’ reviews, and this sometimes leadsto a somewhat redundant treatment ofcertain subjects. However, thisarrangement facilitates the selectivereading of single topics, which isprobably the way this book will be used

most often. Much of the data reviewedhere, of course, come from the majormodel plant Arabidopsis, but whereappropriate, work from other plants,such as Fucus or Antirrhinum, is alsodiscussed.

The first chapter, about cell growth andthe plant cytoskeleton, comes closest toan introduction to the whole book, as it isvery comprehensive and introduces someof the key molecules and mechanisms thatare involved in polarity at the cellularlevel. To some extent, this chapter evenserves as a glossary. Comparisons withpolarity in animal cells make this a goodoverview, and also a starting point forthose interested in more than onekingdom. Here, the reader encountersroot hairs and their growth for the firsttime, and since root hairs are a great

Polarity in Plants: AnnualPlant Reviews, Volume 12Edited by Keith LindseyBlackwell Publishing (2004) 360 pagesISBN 1-405-11432-0£99.50 (hardback)

The Matryoshka dolls of plant polarityMichael Sauer and Jirí Friml

ZMBP, Tübingen, Germanye-mail: [email protected], [email protected]


model system for growing cells, they alsoappear in several other chapters, althoughwith varying success. Chapter 2 attemptsto connect the role of ROPs (RhoGTPasesof Plants) with polar cell-to-cell auxintransport, and contains broad informationabout both topics. Chapter 3 is the last ofthe general chapters, and thoroughlycovers plant cell walls as majordeterminants of the cell’s growth andshape, and their role in polarity. Inparticular, the roles of targeted vesicletrafficking and auxin transport arehighlighted; these and the connection tothe cytoskeleton seem to be the recurringthemes of the first part of the book. Cellwalls are a discriminating feature of plantcells and, with the inherent philosophicaltendencies of Chapter 3, they can indeedbe seen at the ‘transition zone betweenuni- and multicellularity’. With the littleknowledge that we currently have aboutthe molecular mechanisms of polar auxintransport, you can also follow thespeculative notion that the smaller, non-elongating transversal walls of root cellsresemble animal synapses. This otherwisestimulating analogy is brought to itsextreme in Chapter 7, which is on rootpolarity, where these cell walls are almostexclusively referred to as ‘plantsynapses’.

All subsequent chapters focus on specialstructures or processes involving polarity.The reader will learn about trichomes(the little hairs on leaves that are actuallysingle, branched cells), and early eventsin the development of fucoid algae, andwill find an excellent chapter on polarityin Arabidopsis embryogenesis, whichdoes not only review the literature

thoroughly but expands on it in a trulyinspiring way. As mentioned above, thechapter on roots is maybe a bit tooinspired by the idea of auxin behavinglike a neurotransmitter, but otherwise youwill find a thorough review about rootand lateral root development, which alsoconsiders comparisons between differentplant species.

There are no surprises about polarity inthe chapter on the shoot apical meristem,but it does give comprehensiveinformation on the meristem’s amazingself-regulatory capacities. The nextchapter on vascular development ismaybe a bit more substantial withregards to polarity, and is also easier toread. The last two chapters cover lateralorgan and flower development. Itbecomes especially clear in the latter thatpolarity is a phenomenon closely linkedto development. During flower develop-ment, a multitude of polar growth axesemerge, along which floral developmenttakes place. Actually, most forms ofdevelopment do require or lead topolarity, and so it is not surprising thatthis book also serves as quite acomprehensive review of plantdevelopment. As such, this book mightalso prove useful in higher-level graduateclasses, although it is aimed at theprofessional in the field and is certainlynot a textbook. Moreover, the price ofabout £100 will definitely limit theaccessibility of this book to students.

Now, what does the reader learn fromthis book? Overall, it provides a mixedbag of information (a big bag of qualityinformation, that is) that unfortunately

lacks synergy. A useful addition mighthave been a more general introduction orsynopsis of the known mechanisms ofpolarity in a special chapter. This wouldhave helped the reader to see the contextmore clearly and would have improvedsome redundant parts; for example, thoseon the role of the phytohormone auxin.But let us not be greedy but content withwhat we get: a comprehensive and, forthe most part, well-written collection ofreviews that deal with polarity in plants,which, to our best knowledge, can alsoclaim the prize of being the first book onthis topic.

From the concluding remarks of most ofthe chapters, one can infer that still littleis known about the molecularmechanisms underlying polarity.However, there seems to have been arecent boom in identifying molecularplayers involved in cell polarity, and,consequently, any attempt to reviewplant polarity is inevitably condemnedto be slightly out of date, even beforeappearing. A recent major topic in thefield is the polar flow of auxin, which onthe one hand depends on polar, actin-dependent vesicle trafficking of PINproteins and on the other determinespolarity at higher levels. This model waslately reinforced when PIN-dependentauxin flow was identified as a commonplayer in both embryonic and de novoorgan axes formation. However, despitethe recent fast pace of findings in thisfield, there is still a long way to gobefore we have a clear idea about howpolarity is established in plants, and welook forward to a second edition of thisbook in, maybe, five years from now.

5775Book reviews

The vertebrate skeleton is an amazingorgan system. It pleases one by itsexquisite architectural and engineeringbeauty. It impresses by its strength andremarkable adaptability. It is a veritablebeehive of cellular activities: it isconstantly being remodeled by theconcerted action of bone-resorbing and

bone-making cells, and its marrowcompartment serves as a factory forseveral lines of blood cells and adultstem cells. It is a storage facility for Ca2+

and plays an essential role inmaintaining Ca2+ homeostasis in ourbodies. It can fascinate and delight: atrip to any natural history museum with

a group of preschoolers or kindergartenchildren to examine dinosaur skeletonsalmost never fails to generateexcitement. Yet, it can also generate fearas a reminder of our ‘return to dust’, andcan elicit deep concerns as we age andits internal structure slowly becomesosteoporotic and more fragile.

Many scattered bones do not a skeleton makeBjorn R. Olsen

Harvard Medical School, Boston, MA 02115, USAe-mail: [email protected]



The understanding of how this organsystem develops, grows and ismaintained in the adult has come a longway during the past 25-30 years, as aresult of numerous genetic, biochemical,pharmacological, cell biological,biomechanical and clinical studies. Thisexciting advance is documented inmultiple textbooks and review articles,and, of course, in thousands of originalresearch papers. However, for thestudent, postdoctoral fellow or youngscientist who considers entering the fieldof bone biology, navigating through thismass of published information is aformidable challenge. No single textexists that helps the novice to separate‘signals’ from ‘noise’ so that the mostinteresting unsolved problems (the ‘hot’topics) and the most promising emergingtechnologies can be identified. It istherefore with considerable interest oneopens a book that in around 400 pagespromises to represent precisely that typeof text, appropriately titled The Skeleton:Biochemical, Genetic, and MolecularInteractions in Development andHomeostasis. Edward J. Massaro andJohn M. Rogers, the editors of the multi-authored volume, state that their goalwas ‘to provide researchers and studentswith an overview of selected topics ofcurrent interest in bone biology and tostimulate their interest in this fascinatingand diverse field’. Have they succeeded?Unfortunately, after spending some timewith the book I must sadly report that theeditors have not been entirely successfulin this endeavor.

The book is divided into six sections, witheach section split into several chapterswritten by different authors. The sectiontitles broadly reflect the sequence ofevents that characterize the process bywhich most of the skeleton develops inthe vertebrate embryo. In this process,which is known as endochondral bonedevelopment (applicable to the formationof all bones, except for parts of thecraniofacial skeleton and part of theclavicle), mesenchyme forms condensedregions in which cells differentiate intocartilage-producing chondrocytes. Thechondrocytes form cartilage models of thefuture bones, and these models are thenreplaced by bone and bone marrow ina process that couples osteoblasticdifferentiation, angiogenesis andosteoclastic migration with cartilage

removal and bone marrow establishment.Reflecting this developmental sequence,the editors have grouped the chapters intosections as follows: Chondrogenesis,Chondrocytes and Cartilage; Control ofSkeletal Development; Osteoblastic CellDifferentiation; Bone Induction, Growthand Remodeling; Bone Mineralization;and Skeletal Dysmorphology. These arelogical subdivisions of the subject matter,but unfortunately it looks as though theeditors stopped their work at this point. Itis hard to avoid drawing the conclusionthat they did not define a detailedframework for the chapters in eachsection nor provide the authors with clearguidelines for organizing the chapters. Isuspect that they also did not work withthe authors on revising their work toachieve a product that would be as closeas possible to their planned book. Instead,the editors appear to have decided to writea long preface, almost like a mini-reviewof bone biology, in a late attempt toprovide some sort of cohesive structure tothe book. This is not effective. As a result,the book, in my mind, is more like acollection of scattered bones than the kindof treatise on the skeletal organ system Iwas hoping for when I first opened it.

Among the many problems that I canonly blame on the lack of strong editorialhands, is the unexplained variation in thestructure of different chapters. Some arewritten as concise reviews or a series ofmini-reviews (such as chapters 1, 5, 8,10, 14, 18 and 23) – excellent forstudents as an introduction to specifictopics in extracellular matrix and bonebiology. Other chapters (e.g. chapters 4,12, 19, 22 and 24) are organized in theformat of original research papers, withIntroduction, Materials and Methods,Results and Discussion. I suspect thatmost of the data in these chapters havebeen or will be published in moreappropriate peer-reviewed journals in aslightly (or extensively, as the case maybe) modified form. In a third category arechapters (such as chapters 6, 11, 13, 15-17 and 20) that provide a mixture ofreview with a discussion of recent data(with a description of methods andresults) from the authors’ ownlaboratories. I suspect that many of thesechapters have their origins in theBackground and Significance sections ofrecent grant applications.

The quality of the different chapters isalso very variable. This is perhaps to beexpected as they are written by differentauthors, but some editorial interventionwould have helped to make the qualitymore uniform. For example, removingexcess and irrelevant material could havehelped in Chapter 2 (‘Chondrocyte CellFate Determination in Response to BoneMorphogenetic Protein Signaling’). Thischapter contains, appropriately, adiscussion of the bone morphogeneticproteins (BMPs), their receptors anddownstream signaling pathways, but italso contains a table, several pages inlength, of gene mutations that areresponsible for human genetic skeletaldisorders and relevant animal models.Such a table is of course useful, but Icannot understand the rationale forincorporating it in this chapter, and notin, for example, a chapter in the sectionon Skeletal Dysmorphology!

Another example of the lack of editorialintervention is the repetition of the samebasic information throughout manychapters. Thus, after reading about BMPs,their receptors and the downstream Smadproteins, in Chapter 2, the reader is treatedto another description in Chapter 3.

The Skeleton: Biochemical,Genetic, and MolecularInteractions in Developmentand HomeostasisEdited by Edward J. Massaro andJohn M. RogersHumana Press (2004) 428 pagesISBN 1-58829-215-0$150.00 (hardback)

Developmental biology has differentiatedinto a rich, complex field that continuesto progress at breathtaking speed. Thispresents a conundrum for textbookauthors: present students with acomprehensive survey of the entire fieldor distill it down to the essence thatprovides students with a framework onwhich to hang the details andcomplexities. Fred H. Wilt and Sarah C.Hake have chosen the latter approach.Their target audience is students with abasic background in organismal,molecular and cellular biology who donot intend to make developmentalbiology their careers.

Is there a need for such a book? Howwell does it work? Does the book tella compelling story that is as dynamicas the field itself? Would it be capableof corrupting students who neverconsidered a career in development,tempting them to join the ‘dark side’?

The writing style is very accessible,verging on the vernacular, as opposed toa more scholarly style that is standard inmost textbooks. Considering the

intended audience, the style works quitewell. In fact, it is fun to read. Considerthis example from Chapter 3, whichdistills development down to its essence:‘The general “recipe” for animaldevelopment was set forth in Chapter 1:make an egg, cut it up into many diploidcells, move cell groups from place toplace to produce a three layered embryo,and selectively activate gene expressionin different forming tissues and organs’.The rest of the book builds upon thissimple statement. The authors haveelected to feature a limited number ofmodel organisms, rather than taking amore comprehensive approach thatwould use the full palette of organismsthat developmental biologists study. Themarginalization of C. elegans and thezebrafish is unfortunate, but choiceswere necessary to keep the bookreasonably short. All chapters begin witha Chapter Preview, which gives readersthe context and alerts them to the majorconcepts to be covered, and end with asummary of Key Concepts, StudyQuestions and Selected References.Suggested answers to the StudyQuestions can be found at the end of the

book. This provides the book with aninteractive aspect, assuming thatstudents take advantage of theopportunity. An additional interactivetool will be the website, which ismentioned on the back cover of the book,but which was not yet ‘live’ when Iprepared this review.

The book begins by presenting the basicconundrum of development: how can asingle cell, the fertilized egg, give rise toa complex and ordered assemblage ofdistinct cell types that function togetherin the adult, which produces anothergeneration of gametes that contribute toyet another embryonic generation. Theauthors then outline the concept ofdifferential gene expression, usingclassical examples and introducingexperimental approaches that have beenused to study this process. The secondchapter is a brief introduction togametogenesis and fertilization, with aneven more succinct overview of cleavageas an introduction to fate mappingthrough lineage tracing. Given theintended readership, I am surprised thatthe authors did not take advantage of the

5777Book reviews

Repeating important facts is based onsound pedagogical principles, but in thecase of BMPs this principle is taken to theextreme in this book: a basic description ofBMPs and their receptors is repeated inchapters 8, 13, 15 and 16. Editorialintervention would have been very helpfulhere. It may also have helped to improveChapter 3, which deals with chondrocytedifferentiation. Given what we now knowabout the essential roles of the transcriptionfactors Sox9, Sox5 and Sox6 inchondrocyte differentiation, it isremarkable that the discussion in thischapter is almost entirely focused on theregulation of chondrocyte activities in theepiphyseal/growth plate regions ofdeveloping long bones. A detaileddescription of the transcriptionalmachinery required for chondrocyte differ-entiation is entirely omitted! Finally, onehas to ask, ‘editors, where were you?’ when

reading the sentence ‘collagen I consists ofa triple-helix formation’ finds α1(I) andα2(I) collagen chains are described as Iα1and Iα2 chains (Chapter 21) in a book thatcontains an accurate and up-to-date chapteron ‘Molecular Biology and Biosynthesis ofCollagens’ (Chapter 5).

By now it should have dawned on thereader that I cannot give this book twothumbs up. This is the bad news. Thegood news is that although it has too manysharp ‘bones’ to be enjoyed as a full meal,some of the individual ‘bones’ are verygood. The chapters written as concisereviews make excellent reading forstudents and may be useful as readingassignments in introductory courses.Some of the chapters that describemethods and hypotheses will be useful forpostdoctoral fellows and researchers inthe field who would like to achieve better

insights into the experimental strategy andthinking behind the published work fromspecific laboratories. For example,Chapter 7, which describes the use of theloxP/Cre system in targeted mutagenesisof the mouse Hoxd complex, can be readas a supplement to the Materials andMethods section of recent papers fromDuboule’s group. Chapter 26, which dealswith risk assessment issues, will be usefulfor corporate scientists working on animalstudies as part of their companies’submissions to the US Food and DrugAdministration and US EnvironmentalProtection Agency.

The really good news is that theopportunity to write a truly outstandingmodern treatise on the vertebrateskeleton is still open. Until that happens,one will have to select and use parts ofthis book.

Elements of developmental biologyLeon W. Browder

Department of Biochemistry and Molecular Biology, The University of Calgary, Calgary, Alberta T2N 4N1, Canadae-mail: [email protected]



opportunity to discuss reproductivebiology in more detail. I cannot imaginea topic of more interest to universitystudents! Next comes a series ofoverviews of oogenesis and earlydevelopment in Drosophila, frogs, birdsand mammals. In each case, the uniquerole that the organism has played inrevealing developmental mechanisms isdescribed, as well as the distinctivedevelopmental processes employed byeach group of organisms. In themammalian section, the emphasis is onthe mouse, which is the most extensivelystudied mammalian embryo. However, Ithink another opportunity was missed to‘grab’ students’ interest by featuringhuman development more prominently.

The next section of the book featuresvertebrate organogenesis, culminating inmetamorphosis. They precede thediscussion of amphibian metamorphosiswith a discussion of insectmetamorphosis. I suspect that studentswill find this placement a bit confusing.The animal organogenesis section isfollowed by a section on plantdevelopment. It is up to the marketplaceto confirm that there are sufficient non-specialist development courses thatinclude plant development to justify itsinclusion in the book. I hope that this isthe case, because plant development isfascinating and highly relevant.

The remainder of the book is devoted torevisiting topics that are beenintroduced in earlier chapters anddiscussing them in depth from a cellularand molecular perspective. Some planttopics are interspersed among mostlyanimal topics. The first two of thesechapters deals with the cellular basis ofmorphogenesis: how do cells organize

themselves into a complex, functionalorganism? Once again, the authors havemissed an opportunity here. In this case,the discussion of cell motility is notcomplemented by a discussion ofmetastasis. I think it is instructive torelate academic topics to topics that arerelevant to our daily lives – particularlyin a book targeted to non-specialists.The final section of the book deals withthe regulation of gene expression,returning to the conundrum presented atthe outset: how do cells with identicalgenomes become so very different fromone another during development? Thebook culminates in a fascinatingchapter on ‘evo-devo’.

In summary, this is a noble effort that iswell written. There is a need for aslimmed-down overview of developmentthat is accessible to students who do notintend to specialize in the field. However,I would have preferred a book that didmore to emphasize the relevance ofdevelopmental biology to them.Reproductive biology, cancer, tissueengineering, and reproductive andtherapeutic cloning are topics thatfascinate us all. We owe it to our studentsto inform them about them. It is easier todo that if their course textbook providesa foundation for the understanding ofsuch topics.

To give you the bottom line first: thisbook is a masterpiece written bynumerous masters who are able to ‘speakdifferent languages’ and who bridgedisciplines from developmental biology,normal and abnormal morphogenesis,and molecular biology, to clinicalgenetics and dysmorphology.Understanding developmental biology isa crucial requirement for those workingin clinical genetics; and the two fieldsare now coming together throughadvances in the Human Genome Project

and in elucidating the genetic basis ofvarious genetic disorders. I myself feelprivileged both to work with familieswho have a child with a severe birthdefect and at the same time to direct alaboratory whose research focuses onidentifying the underlying basis ofnormal and abnormal embryonicdevelopment in humans.

Our knowledge of developmentalpathways is still in its infancy comparedwith what is known about biochemical

pathways. The editors have accomplisheda monumental task by putting togetherchapters on the large number of humanmultiple malformation syndromes thatare known about and organizing themwithin developmental pathways. This isthe first time human developmentaldisorders have been covered in this wayin a textbook. As mentioned in thepreface, the idea for Inborn Errors ofDevelopment was influenced by Garrod’sconcept of inborn errors of metabolism,which has been expanded on here to

From developmental genes to dysmorphology: human developmentat its bestMaximilian Muenke

Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-1852, USAe-mail: [email protected]


Principles of DevelopmentalBiologyBy Fred H. Wilt and Sarah C. HakeW. W. Norton & Company (2004) 430 pagesISBN 0-393-97430-8$90.00 (paperback)

5779Book reviews

inborn errors of development. If the goalof this book is to integrate clinical geneticdisorders with molecular findings to placethese in the context of development, it isa goal that has been clearly accomplished.This does not come as a surprise, as all ofthree editors, and many of thecontributing authors, are clinicians aswell as bench scientists.

The book begins with an overview ofsome general concepts, with introductorychapters on approaches to understandingcongenital malformations, generalprinciples of differentiation andmorphogenesis, and the role of modelorganisms in understanding development.The chapters that follow detail patterns ofdevelopment of various organ systems.Most of the chapters of this book aredevoted to over 100 clinical geneticdisorders for which the underlying causeshave been identified. These includedisorders caused by anomalies in genessuch as sonic hedgehog (SHH), WNT,transforming growth factor β, tumournecrosis factor, fibroblast growth factorreceptor and Notch. Disorders that arecaused by mutations in genes or genefamilies that have uncertain or unknownpositions in a developmental pathwayinclude members of the HOX, PAX,Forkhead and the T-box gene families.The book concludes with chapters onnumerous genetic disorders that arecaused by changes in genes that encodeproteins involved in the regulation ofchromatin structure and gene expression,and in transcription, post-translationalcontrol and ubiquination, and in those thatencode guanine nucleotide-bindingproteins, kinases and phosphatases. Manyof the disorders resulting from mutations

in the latter are tantalizing, as they affectmultiple organ systems in common andrare dysmorphic syndromes. Only nowthat their underlying molecular basis isknown, does the combination of clinicalfindings make sense.

An area close to my own research interestis cholesterol biosynthesis and SHHsignaling, which is very well covered inthis book. SHH signaling is a primeexample of a well-defined pathway that iscritically important during earlyembryogenesis and is specifically requiredin limb and brain development. As thebook discusses, abnormal SHH signaling

can lead to disorders that affect differentorgan systems, such as Smith-Lemli-Opitzsyndrome, a birth defect that is caused byabnormal cholesterol biosynthesis. Lossof function of SHH can cause the mostcommon forebrain anomaly in humans,holoprosencephaly. Loss of function ofPATCHED1, the receptor for SHH, leadsto basal cell nevuscarcinoma or Gorlinsyndrome. And distinct disorders withanomaliesof the hands and feet,such as Pallister-Hall and GreigCephalopolysyndactyly syndromes, arecaused by mutations in GLI3, anothergene in the SHH signaling pathway.

This book is written for healthprofessional and basic scientists alike. Ilearned that it is already used as a textbookin developmental biology classes. As thedirector of medical genetics training atNIH, I will recommend this book toclinical and PhD fellows in my program.At the same time, I also recommend it tothe connoisseurs of dysmorphology – mycolleagues from the David W. SmithWorkshop on Malformations andMorphogenesis. I have no doubts that thisbook will become one of the standardtextbooks, comparable with (yet uniquelydifferent from) other classics by Jones,Scriver et al. and Gilbert (Jones, 1997;Scriver et al., 2001; Gilbert, 2000).

ReferencesGilbert, S. F. (2000). Developmental Biology, 6thedition. Sunderland, MA: Sinauer Associates.Jones, K. L. (1997). Smith’s RecognizablePatterns of Human Malformation, 5th edition.Philadelphia, PA: W. B. Saunders.Scriver, C. R., Beaudet, A. L., Sly, W. S. andValle, D. (eds) (2001). The Molecular Bases ofInherited Disease, 8th edition. New York, NY:McGraw-Hill.

Inborn Errors ofDevelopmentEdited by Charles J. Epstein, RobertP. Erickson and Anthony Wynshaw-BorisOxford University Press (2004) 1082 pagesISBN 0-19-514502-X£150.00 (hardback)

The first edition of Ralph Greenspan’sfly-pusher’s hand-book appeared in1997 and was an immediate hit becauseit filled a gap. At that time theDrosophila field was booming as never

before, and new people were taking upthe way of the fly. There were of courseexisting books on Drosophilamethodologies but these were eitherdated (e.g. Demerec, 1950; Roberts,1986), or comprehensive and beyond thedigestive capacity of the larval fly-

pusher (Ashburner, 1989b; Ashburner,1989a). The Greenspan book grew fromhis teaching (at Cold Spring Harbor andon various university courses), and wasbeautifully written and accessible tobeginners. We ourselves have used it asa first resort: telling any new student or

‘Remember Irena: flies are not freedom’*Edward M. Rogers and Kevin Moses

Department of Cell Biology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USAe-mail: [email protected]


*Misquote from Martin Cruz Smith’s Gorky Park.


visitor to the lab to go away and read itbefore asking a lot of questions. We canattest to its popularity: it is the moststolen book from the office and we musthave bought six copies by now. In fact,when we went to the shelf for the 1997edition to prepare this review, it wasgone, and we had to borrow one from apost-doc who happened not to be at hisbench. He will get his copy backtomorrow, promise!

The 1997 edition dealt with the basics offruit-fly technology in seven chaptersand 126 pages of text. The new editionstill has only seven chapters, but it hasgained weight (22 more pages). Manynew fly people are also new geneticists,and this book starts at the beginningwith basic explanations of the majorphenomena of classical genetics (it isvery light on molecular biology). Evenfor people coming in from other geneticsystems, there is still the barrierof nomenclature and the sheersophistication of fly genetic tools, manyof which have no equivalent in otherorganisms. Greenspan does an out-standing job of making things plain.

The first chapter explains how to docrosses, even telling the reader how tocollect flies. Mutant and gene names areexplained, as are the chief glory of flygenetics: the balancers (chromosomeswith markers and multiple inversionsthat allow us to manipulate genotypeswith relative ease by preservinghaplotypes). Greenspan adds a newexplanation of why genes and mutationsthat have been re-identifed should retainthe name first given to them in theliterature. Sometimes large egos renamegenes, and this leads only to confusion.

The second chapter discusses techniquesfor isolating new mutations in new orknown genes. Good descriptions ofchemical, radiation and transposonmutagenesis are preserved from the firstedition, as are the crossing schemes thatcan be employed. Also included aredescriptions of ‘enhancer trapping’,which allows one to detect genes bytheir expression patterns (a techniquenow in vogue in mice and fish). Newmaterial includes two new techniquesfor ‘reverse’ genetics in the fly:obtaining genetic mutations in genesknown from molecular data (now

usually the genomic DNA sequence).These are homologous recombination(long developed in yeast and mice),which has been done a few times in thefly and is quite clever but also arduous,and RNA interference, which is wellestablished in worms. The latter hassome drawbacks (it’s hard to get acomplete null) but has become verypopular. Clearly, reverse genetic toolsare required to exploit the genome dataand these are important additions to thebook.

The third chapter is on mappingmutations and retains good descriptionsfrom the first edition on classictechniques, as well as details of newertricks. One item has gone: polytenechromosome in situ hybridization. Thiswas a beautiful technique and achallenge to master. It is sad for us toadmit that something that we learnedhow to do is now really obsolete (alongwith running sequencing gels andchromosome walking), but Greenspan isright: nobody does this anymore.Nowadays, new P-element insertions,for example, are mapped instead bysequencing flanking DNA and findingthe short sequence in the genome

computationally. Although forwardgenetic screens are a strength of the flysystem, assigning the recoveredmutations to specific genes known in thegenomic sequence remains slow. The‘new-tech’ approaches to mappingdescribed in the new edition of the bookhave made a significant difference. Theissue is one of getting phenotype-basedmapping down to a very fine scale.Greenspan describes how to do this infour ways, three of which depend on theincreasingly dense forest of known andcharacterized P-element transposoninsertions. The simplest is by fine-scalemeiotic recombination using transgenicmarkers (usually a wild-type whitegene), which, in the case of lethals,comes down to looking for the rarewhite-eyed flies in a pile of red (ororange) ones and counting both piles –a trivial task. This is great until you getvery close to the mutant, when the pileof red-eyed flies may become huge. Thesecond way is to use site-specificrecombination, in which the position ofthe cross-over is pre-determined(usually at the chromosomal locus of aspecific transgenic P-element). Becausethe position of the cross-over is nowfixed, the frequency of the cross-over isindependent of the distance between thetransgene and the mutation, and thus thetechnique only gives the direction fromthe cross-over point to the mutation(using an outside marker). This worksfor just fine for very small distances, andso becomes very useful as you get closeto the mutant. Thirdly, when P-elementsare excised from the chromosomeduring transposition, they often tear offsome additional DNA, and Greenspandescribes how to derive small deletionsby inducing this imprecise excisionfrom a P-element that resides close tothe mutation. The fourth approach doesnot depend on P-elements, but usessequence polymorphisms as markers.This last seems onerous (you have tosequence), but is likely to become morepopular as tricks for detectingpolymorphisms improve.

Chapter 4 is almost unchanged from theprevious edition and deals with theconstruction of genotypes (chromosomejuggling). The fifth chapter is also littlechanged, but is really crucial – we wishit were first! This is a consideration ofthe different types of mutation as first

Fly Pushing: The Theory andPractice of DrosophilaGenetics, 2nd EditionBy Ralph J. GreenspanCold Spring Harbor Laboratory Press (2004)191 pagesISBN 0-87969-711-3£39.99 (paperback)

5781Book reviews

defined by Herman Muller (Muller,1932). The idea of a null mutation,versus partial loss of function, versusseveral kinds of gain of function arediscussed, as well as how to tell thedifference between them. This is reallyimportant because the interpretation ofthe function of a gene in the biology ofthe fly often relies on what sort ofmutation you have. For example, amutation that is recessive and confersextra wings (such as some combinationsof bithorax mutations) might lead you toconclude that the normal and solefunction of the wild-type gene is tosuppress the growth of extra wings.However, in this case, later study ofcomplete nulls (mutations of the samegene, with no protein expression at all,called Ultrabithorax) upset the theoryand revealed that the gene has a muchbroader and more basic role indetermining the identity of segments.

The fifth chapter also explainsconditional alleles (usually temperaturesensitives), and how they can arise.These are of increasing importance asthey are one of the few ways we canstudy the (often many) late functions ofgenes required early for cell viability orproliferation. The clearest case thatGreenspan discusses is that of Notch,which is involved in an enormousnumber of developmental decisions;without the Notch temperature-sensitivemutation we would only know about afew of these.

The sixth chapter considers anotherleading fly tool: the construction of

genetic mosaics so that only a part of theanimal is mutant, or overexpresses agene, or even both! There are techniquesfor inducing such mosaics at randompositions, or in specific places, and formarking them positively or negatively(so that the mutant cells either loose orgain some marker, such as the GreenFluorescent Protein). Again, this is anarea in which the fly is far ahead of othersystems. The book ends with a briefchapter encouraging the new‘Drosophilist’ to go forth and prosper.The initial effect of this avalanche oftechnology is bound to be daunting forthe new fly-person, but if they takeGreenspan’s advice and get started withsomething easy, expertise will follow.

Although the book is really excellent,it’s not perfect and three importanttopics are left out, so we will continueto have to explain them to new labmembers. While Greenspan does a goodjob of explaining what null andconditional mutations are, he doesn’texplain how to get them. Given theimportance of nulls, the common P-excision technique should have beenexplained in this context. The secondomission is how we can really nail downin which gene a mutation really lies: i.e.going from genetic mutant to molecularlocus. This used to be called ‘cloning’the gene, but it is really the end-point ofmapping. We agree with Greenspan inthinking that fly screens are really ourgreat gift to other systems – but we arenot finished until we can identify ourmutations as being in a specific gene.This can be done in a few different ways

– usually the best is by transgenic rescue– but for some reason Greenspan doesnot discuss the topic conceptually, ordescribe how fly transgenics are made.The third topic that we really wouldliked to have seen is a description of theresources available to fly workers: thestock center and the databases.Drosophila benefits hugely from awealth of free (or almost free) materialand information, but the ground-rulesfor getting it are not obvious (FlyBasesearches are sometimes quite tricky),and some basic and clear explanations ofthe conventions and places to startwould have been really useful.

Overall, the first edition of this book wasa hit and we are confident that thesecond will be also. New techniqueshave been added while retaining theaccessibility of the previous version.We’re sure we’ll have many copies ofthe second edition stolen off our shelvesin the future. We had better order six.

ReferencesAshburner, M. (1989a). Drosophila: ALaboratory Handbook. New York: Cold SpringHarbor Press.Ashburner, M. (1989b). Drosophila: ALaboratory Manual. New York: Cold SpringHarbor PressDemerec, M. (1950). Biology of Drosophila. NewYork: John Wiley and Sons.Muller, H. J. (1932). Further studies on the natureand causes of gene mutations. In InternationalCongress of Genetics, Vol. 1 (ed. D. F. Jones),pp. 213-255. Brooklyn, NY: Brooklyn BotanicGarden.Roberts, D. (1986). Drosophila: A PracticalApproach. Oxford, New York, Tokyo: IRL Press.

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