Multicellular organisms coordinate their growth, development and homeostasis through cell-cell communication mediated by a relatively small number of extracellular signaling molecules, often referred to as growth factors. Nowadays, it is difficult to open a new volume of a developmental biology journal and not find at least one article describing the role of growth factor signaling in a developmental event. It is safe to expect that most developmental decisions involve growth factor signaling. For this reason,it is no longer sufficient to show that a growth factor is involved in a developmental event. Instead, current and future growth factor signaling research should focus on how growth factors mediate such varied effects on cells during development, growth and homeostasis. In other words, why does a particular growth factor mediate a mitogenic response in one cell, but a survival effect in another, or a migratory effect in another, or a change in fate in yet another. Thus, in my view, the exciting current and future work being done in the broad field of growth factor signaling involves investigating how growth factor signaling is modulated in space and time, and how cells interpret the signals appropriately and in a coordinated fashion. This level of understanding is essential for us to truly understand not only how growth factor signaling coordinates development, but also how and why failures in this coordination result in disease states, such as cancer and congenital abnormalities.FIG1 

Analysis of Growth Factor Signaling in Embryos
 Edited by Malcolm Whitman and Amy K. Sater
 Taylor and Francis (2007) 435 pages
 ISBN 0-8493-3165-X
 £92 (hardcover)

Analysis of Growth Factor Signaling in Embryos
 Edited by Malcolm Whitman and Amy K. Sater
 Taylor and Francis (2007) 435 pages
 ISBN 0-8493-3165-X
 £92 (hardcover)

I found the book very useful and I am happy to have a copy in my office. However, I cannot say that the book is wholly inclusive

Historically, much effort has gone into investigating growth factor signaling in tissue culture assays. However, it is difficult to imagine that a deep understanding of the details of growth factor signal modulation and interpretation can be achieved by studying them in cell lines, in particular when addressing multicellular and even multi-tissue processes, such as morphogenesis. When tackling these difficult questions, it is embryos that have much to teach us, as they provide a more physiological, in vivo context in which to investigate the complexities of growth factor signaling. The question is: how does one tease out the secrets of the intricacies of growth factor signaling from embryos? The book, Analysis of Growth Factor Signaling in Embryos, edited by Malcolm Whitman and Amy Sater, aims to provide the theoretical and technical framework to investigate how growth factor signaling is modulated and coordinated in embryos. The book is divided into four sections: (1) Signals and Pathways; (2) Ionic Signals; (3)Transcriptional Regulation of Target Genes; and (4) Emerging Strategies for the Analysis of Signaling in Development.

The first section of the book contains seven chapters, devoted to what could be most conventionally described as growth factor signaling in embryos. It covers a chapter (Chapter 1) on the study of canonical Wnt signaling by Wilson K. Clements and David Kimelman; a chapter (Chapter 2) on non-canonical Wnt signaling by Michael Kühl and Randall T. Moon; and a chapter (Chapter 6) on Wnt signaling through Rho-family members by Raymond Habas and Xi He. Thus, Wnt signaling is very well covered in the book. There is only one chapter devoted to the study of TGFβ signaling (Chapter 3). This chapter,written by Shailaja Sopory and Jan L. Christian, is devoted to the analysis of proprotein processing during the activation of TGFβ ligands. This chapter is interesting, but I would have expected at least another chapter on the modulation of TGFβ-family signaling by extracellular inhibitors (such as noggin and chordin during BMP signaling), or perhaps one on the regulation of Smad activity by the Nodal/BMP pathways in conjunction with other pathways. There is no chapter devoted to general receptor tyrosine kinase (RTK)signaling (such as FGF, PDGF, EGF, Ephrin, neurotrophins), which I think is lacking. However, there is a very good overview (Chapter 4) on the analysis of MAP kinase pathways in embryos, written by Amy K. Sater and Heithem M. El-Hodiri. There is also a comprehensive overview of retinoic acid signaling(Chapter 5) by Malcolm Maden. Malcolm Whitman's chapter (Chapter 7) is devoted to the use of phosphospecific antibodies to query the activation state of signal transduction pathways in embryos, either by western blots or in situ,using whole-mount immunohistochemistry.

The second section only has two chapters: one devoted to calcium signaling by Diane C. Slusarski (Chapter 8) and the other devoted to biophysical or electric fields by Dany S. Adams and Michael Levin (Chapter 9). These chapters would not be commonly thought of as fitting neatly under the growth factor signaling umbrella, but I am very pleased that they were included. Growth factor signaling can obviously lead to a calcium response, but so can other events, such as fertilization. However, there is no doubt that embryos are ideal systems in which to study the complexities, roles and regulation of calcium signaling in an in vivo context. The chapter on biophysical signals by Adams and Levin is, without question, the most significant chapter in the book. For one, it covers 85 pages, although admittedly, 29 pages are devoted to appendices and 17 pages to references. But perhaps the most useful aspect of this chapter is to force those of us who tend to ignore electric fields or biophysical forces in biology to take note and to open our eyes, as there are signaling mechanisms in development beyond those mediated by conventional growth factors.

The third section contains two chapters, which are devoted to the transcriptional readout of signaling in embryos. Chapter 10, written by Curtis Altmann, describes the use of expression profiling in embryos and Chapter 11,by Daniel R. Buchholz, Bindu Diana Paul and Yun-Bo Shi, describes how to perform chromatin immunoprecipitations from material isolated from embryos and tadpoles. The final section contains four chapters, which are loosely brought together under the heading `Emerging Strategies'. Chapter 12, written by Joanne Chan and Thomas M. Roberts, is devoted to the use of chemical compounds to investigate growth factor signaling during embryogenesis. More specifically, the chapter describes how one can use chemical compounds to study vascular development in zebrafish and, conversely, how zebrafish can be used to help identify chemicals with potential value in the treatment of human disease. Perhaps along the same general line, Chapter 14, by Karen J. Liu,Jason E. Gestwicki and Gerald R. Crabtree, describes how one can generate conditional alleles for the protein of your choice, which is activated by small molecules, a very useful technique indeed. Chapter 13, by Karen Symes,provides an overview of how one can study the cellular movements of gastrulation, with the hope of beginning to understand how growth factor signal inputs from many different pathways come together to coordinate a process, which is mind-boggling in its complexity. In the end, we need to start thinking of growth factor signaling in the context of the whole embryo. Each signaling pathway is likely to feed into other pathways, and the responses will sometimes be positive and sometimes negative, and all this has to be coordinated within and between the cells correctly. Clearly, this will turn out to be a very complicated network, which must be modeled so that a deeper understanding can emerge. Thus enters the field of systems biology, and the final chapter of the book, written by Gregory R. Hoffman, Kevin Brown,Adrian Salic and Ethan Lee, which describes how one might start modeling signaling networks in development.

Overall, I found the book very useful and I am happy to have a copy in my office. However, I cannot say that the book is wholly inclusive. There is much that it covers, but there is much that is lacking. For example, the book fails to mention or describe work on Notch signaling, Hedgehog signaling, or on the great plethora of signaling by RTKs. Thus, the book is rather biased in the selection of growth factor signaling that it covers. Another clear bias in the book is in its coverage of experimental organisms, which is mostly of the frog, Xenopus laevis. In my laboratory, we use Xenopus to investigate growth factor signal modulation, as it provides a powerful system in which to combine large-scale functional genomic screens with biochemistry,cell biology and embryological manipulations. However, I certainly would not say that it is the only useful system in which to study growth factor signaling in embryos. Zebrafish gets a mention in several chapters, but it only features exclusively in one chapter (Chapter 12, entitled `Chemical Biology in Zebrafish Vascular Development'). Is this enough? I would expect my zebrafish embryology colleagues to be of the view that it is not. Chick embryos are mentioned in Maden's chapter and in Adam and Levin's chapter, but elsewhere they fail to feature at all. Again, my chick embryology colleagues might be disappointed. Invertebrate models, such as Drosophila, C. elegans and ascidians, are missing altogether. Again, this is an unfortunate failing in the book. However, for what it does contain, the book is very good. I would suggest that every laboratory working on growth factor signaling in Xenopus should get one, as should any laboratory planning to work with Xenopus.