J. Anat. (1997) 190, pp. 631–632. Printed in Great Britain 631

Book Reviews

Extracellular Regulators of Differentiation and De-

velopment. Biochemical Society Symposium, no.

62. Edited by K. C, S. P. J, D. G.

W and G. G. L. Pp. xiii­176; illus-

trated; £65 hardback; ISBN 1 85578 070 4.)

London: Portland Press. 1996.

Generation of form and pattern in the developing embryoinvolves the integrated control of cell proliferation, differen-tiation and morphogenesis. Research into the nature ofthese processes was, during the late 1980s and early 1990s,dominated by the discovery of new genes whose patterns ofexpression suggested that their protein products are involvedin developmental mechanisms. This descriptive phase hasprovided a sound basis for investigations of how these geneproducts themselves induce changes in gene expression andhence further differentiation and morphogenesis. Many ofthese events involve interactions between ligands andreceptors. The two major extracellular signalling systemsinvolve either ligands which are synthesised in cells close tothose of their receptor, or circulating hormones, includinghormone-like molecules derived from maternal dietaryprecursors (vitamins A and D). The receptors are eithertransmembrane proteins whose activation sets off a chain ofcytoplasmic events leading to the nucleus, or nuclearreceptors that are directly involved in the transcriptionalprocess.

Progress in this field was recently celebrated by aBiochemical Society Symposium, the proceedings of whichare now published under the title Extracellular Regulators ofDifferentiation and Development. This is a timely book, andalthough there have inevitably been some significant newdiscoveries since the symposium, it is and will remain forsome time a good source of information. It is also a wellorganised book, taking us from peptide growth factors inrelatively simple developmental systems, to retinoids andtheir receptors in the context of mammalian cardiovascularmorphogenesis. The variety of systems covered is refreshing:in addition to embryonic development, there are two articleson metamorphosis and one on regeneration. Both of theseprocesses depend on nuclear receptors and their ligands. Itwas fun to discover that current understanding of the role ofthe steroid hormone ecdysone in Drosophila developmenthas followed progress in steroid hormone research inmammals ; in discoveries of evolutionary conservation in themolecular control of development, Drosophila tends to leadrather than follow.

Most of the articles in this book are written in a style thatis accessible to the nonspecialist, including the non-biochemist. An aspect that I particularly liked is that inattempting to present their work to a general readership,many of the authors have considered the general principlesthat are illustrated by the system they are investigating. Ingeneral, the level of success in these important aspects ofwritten communication is inversely proportional to thenumber of authors.

Early in development, maternal factors play importantroles. Slack and colleagues describe the experimentalevidence for their conclusion that fibroblast growth factors(FGFs) of maternal origin are involved in mesoderminduction through their upregulation of vg1, an activin-likemember of the TGFβ family, which is the primary inducer.

Many developmental mechanisms discovered in one systemare found to have equivalents in quite different contexts,and I was particularly interested to read that it is FGF’s low‘tonic ’ stimulus of the signal transduction pathway thatmakes the animal hemisphere of the embryo competent torespond to activin-like factors, whereas later events in-volving FGFs require higher levels of ligand. The effects ofactivin are similarly concentration-dependent, and similarlyvaried, to those of FGFs: Zimmerman & Mathews showthat in addition to their involvement in early embryogenesis,activins are involved in the regulation of hormone pro-duction, promotion of erythrogenesis, regulation of cellcycle events, modulation of neuronal differentiation andbone growth. It is precisely these pleiotrophic aspects ofsignalling molecules that makes it essential for anyoneinterested in this field to take a broad approach.

Vertebrate limb development is a favourite system fordevelopmental biologists ; it is represented in this book byapproaches through three different signalling systems, andone account of studies on regeneration. Abud and colleaguessummarise recent work that has given spectacular ex-perimental support for the hypothesis that FGFs playfundamental roles in the induction of limb buds from theembryonic flank. The observation that mouse embryoschimaeric for constitutive FGF-4 expression form fin-fold-like structures between the fore and hindlimb buds isparticularly intriguing. It is disappointing that the chimaeraapproach did not result in sustainable limb development(the buds lacked an apical ectodermal ridge), in contrast tothe FGF-soaked bead approach used in the chick. Recentadvances in understanding the role of Sonic hedgehog (Shh)in patterning the anteroposterior (craniocaudal) axis of thelimb is summarised in the article by Marigo and colleagues,including experimental evidence for its induction of the 5«HoxD genes and Bmp-2. These Shh-dependent events alsorequire Fgf-4, which is synthesised in the apical ectodermalridge. Details of the Shh receptor have been published sincethis review was written, but their absence does not detractfrom the usefulness of this account. Thirdly, Sucov andcolleagues describe the interesting observation that the wellknown effects of retinoic acid (RA) excess in inducing limbdefects in the mouse are transduced by the nuclear receptorRXRα.

Questions concerning the roles of RA in development andregeneration have for many years been dominated by anexperimental approach using exogenous RA, often atunphysiologically high levels. The field has now progressedto investigation of the physiological roles of RA; the majormethods are molecular manipulation of the receptors, asexemplified by Sucov and colleagues, and the induction ofvitamin A deficiency (not included in this volume). JeremyBrockes has taken a different approach in his studies on theregenerating amphibian limb, in which exogenous RA isable to alter the axial level of the regenerating structures. Hehas injected reporter cells into the blastema of the amputatedstump, and shown that the injected cells become incor-porated into the blastemal mesenchyme, where theyparticipate in all the normal proliferation and differentiationevents of regeneration. This approach has shown thatintrinsic RA activity is increased in the blastema duringregeneration, that the source of RA is the wound epidermis,and that the strength of RA activity is directly related to theaxial level at which the blastema forms. The use of chimaeric

632 Book Review

receptors has further indicated that the effect of retinoic acidis direct, using a specific receptor. The question now beingpursued is how this signalling process is translated intopositional information. The level of understanding of thepatterning role of RA already achieved here is greatly inadvance of that for any other morphogenetic system; thiswork is a model for the fruitful integration of molecular andsurgical approaches to fundamental developmental prob-lems.

It is not possible to do justice to all the articles in thisexcellent volume. The book ends with a brief reference tooverlap between the FGF and RA signalling systems, in thereport by Old and colleagues that RA induces a novelmitogen-activated protein kinase phosphatase (a moleculethat can modulate signal transduction from cell surfacereceptors that act via the MAP kinase pathway). But it isJamshed Tata, in his article on metamorphosis, who bestsummarises the integrative nature of all the signallingmechanisms addressed in this book: ‘As cross-talk systemsbecome better defined at the molecular level, it will becomeincreasingly clear that complex intracellular networks ofhormonal and non-hormonal signals facilitate a well-co-ordinated and homoeostatically controlled regulation ofgrowth and development’. To work on extracellular factorsand receptors in the context of signalling systems inembryonic development, one must keep an eye on the wholefield; this book provides an excellent perspective.

-

Clinical Anatomy, 3rd edn. By E W. A. (Pp.

xv­372; illustrated; £16.95 paperback;

ISBN 0 683 06199 2.) London and Baltimore:

Williams and Wilkins. 1997.

There are, of course, vast numbers of textbooks of anatomyfor medical students, let alone those designed for dentists,nurses, and other specialist groups. This particular one, nowappearing in its 3rd edition, forms part of a large groupentitled ‘National Medical Series for Independent Studies ’which covers basic sciences and clinical subjects for medicalstudents. The publisher states that the first objective of thisbook is to facilitate the study and review of human anatomyand is aimed at the United States Medical LicenceExamination Step I. Its author, a professor of anatomy andcell biology at the College of Physicians and Surgeons ofColumbia University, New York, has produced an intensivetext : a mass of information in small type and in note fromwith numerous line diagrams and supplemented by manyand extensive tables. The whole field of macroscopicanatomy is covered and each section ends with a largenumber of questions, mostly based on clinical problems,with ‘yes or no’ answers provided and the correct answersthen discussed.

This book has obviously been a proven success in theUnited States. Its very condensed format is unlikely toappeal to medical students in the United Kingdom, althoughthey could find its highly concentrated note format useful forrapid reference.