NATO-Lim bo-Devo-Evo Developmentul Putterrzing ofthe Vertebrate Limb (NATO AS1 Series A: Life Sciences Vol. 205) (1 99 1). Edited by J. RICHARD HINCHCLIFFE, JUAN M. HUKLE AND DENNIS SUMMERBELL. Plenum Publishing Co., New York and London. $1 15 in USAICanada, $138 outside, f82.65 UK. Pp . xi+452. ISBN 0-306-43927-1. By Jonathan Cooke Knowledge of cellular and molecular events in the vertebrate limb rudiment has burgeoned recently in parallel with devel- opmental biology generally, and the workshop whose pub- lished proceedings compose this volume may just have caught the first exciting intimations as to the central genetic mechanism controlling limb pattern. In addition to this the particular traditions of work on limb development, in con- trast perhaps with the equivalent traditions for whole-body pattern development in the slightly younger embryo, have meant that there is now a rich set of data on changes in extra- cellular matrix, growth factors etc. available for the limb. Finally, limbs have become one of the happiest hunting grounds for evolutionary developmental biologists of both the speculative and the harder-nosed varieties. For all these reasons the organising, editing and final production in as coherent and digestible a form as possible of this workshop and book was a bravely undertaken task. Those responsible deserve congratulation for the extent to which they suc- ceeded.

Before conveying an impression of the ground covered, and of the conclusions one is left with, I cannot resist ques- tioning the role of such lengthy and specialised (and, unavoidably, internally repetitious) publications in rapidly developing scientific fields, especially in times of cash- starved libraries and personal pockets. I suppose someone in the course of writing a massive and definitive course text for development generally could, as it were, digest such a book as this into a section of theirs, with the hope thereby of being more up to date or complete than their own reading of pri- mary literature would have allowed. But as I began by hint- ing, reliance on this volume for such a purpose, even begin- ning at the moment of its publication, would miss out on the most exciting functional correlations between specific genetic, and murphogenetic, activities in limb rudiments, that have come along since. Otherwise, the set of all serious buyers and perusers of this book must surely extend little beyond the long and international list of attendees and their own research students, As a physical object, its utility has not been helped by the camera-ready publication technique which leads to a diversity of appearances of the different, texts, and often a difficulty in rapidly distinguishing figure legends from preceding text when reading. Surely with elec- tronic desktops now standard, the resources of NATO could somehow escalate to give a inore felicitous texture to their publications.

Major sections of the meeting proceedings, which appro- priately carved up this diverse field, are each prefaced by an overview from a longstanding researcher which guides read- ers into what is to come, as well as being a justifiable sound- ing board for his opinions as to what is important. In the first

section are collected those components of the system that together have the best claim to be separatcd out conceptually as ‘the mechanism’ of laying down the large-scale limb pat- tern. These are the intercellular positional signalling system, into which retinoids and their effects are currently OUI best (though problematic) avenue of entry, and the intracellularly acting HOX (-containing homeoboxes homologous with the Drosophila antennapedia-like ones) gene clusters that may record and encode positional value. The main excitement here is that everything now suggests that one as yet not-quite- understood interaction, involving the localiscd activity of a retinoid, the progressive activation of HOX genes within each cluster, and ‘growth’ or ‘time’, is responsible first for laying down the axial body plan and then, by its more local repetition, for elaboration of limb pattern within each rudi- ment, Conceptually - although the details may have sur- prised him and us -this is exactly as theoretically proposed a quarter-century ago by Lewis Wolpert, still active in the experimental limb field. For anyone unaware of this emerg- ing story, this section of the book alone is well worth reading in its entirety as a preparation for understanding the succeed- ing two years’ exciting papers.

If the details of chondrogenesis, myogenesis, and exlracel- lular matrix and growth factor deployment dealt with in the middle section seem less central, they may nevertheless be at least as imporlant as future handles on medical intervention and repair etc. Furthermore, there has to be something partic- ular to the cell biology in the zone immediately underlying the apical ectodermal ridge of limb buds, the ‘progress zone’ of pattern elaboration as they grow, that & central to the fun- damental mechanism. The chances are that this will lie within the areas of ccll biology dealt with in this section, which benefits from good terminal as well as initial review contributions.

Finally, what of evolution and all this? The field of ‘Devo- Evo’. to give it its current transatlantic tag, has always frus- trated me by seeming to promise the greatest fascination of all, while in the event often proving disappointing with intel- lectual fuzziness and a sort of intangibility. It remains fraught, and characteristically variable in quality - it seems no accident that in this section of the book alone I found the one or two entire chaptess whose inclusion seemed to push its covers further apart without increased benefit to the reader - but there is now much of real fascination. I would say on the basis of this final evolutionary section that it is within the ver- tebrate limb field that Devo-Evo will first come of age and acquire density of substance. And this is important because, if it is to pass beyond empty games about selfish genes, Evo- lutionary Biology must become Evolutionary Developmen- tal Biology. How do changed genes viably change organ- isms’ forms? We may soon have a chance to know.

Jonathan Cooke, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA.