Morphogens, Compartments, and Pattern: Lessons from Drosophila?

Peter A. Lawrence* and Gary Struhl† Epigenesis, at least in Drosophila, depends on three steps which interlock and overlap; we simplify and refer *Medical Research Council Laboratory of Molecular Biology to these as the “central dogma.” First, positional information in the form of morphogen gradients allocates Hills Road Cambridge CB2 2QH cells into nonoverlapping sets, each set founding a compartment (Garcia-Bellido et al., 1973; Lawrence, 1973). United Kingdom †Howard Hughes Medical Institute Second, each of these compartmentsacquires a genetic address (Garcia-Bellido et al., 1979), the combination Columbia University College of Physicians and Surgeons of active and inactive “selector” genes (Garcia-Bellido, 1975) that tells the founding cells and their descendents 701 West 168th Street New York, New York 10032 not only which part of the body to make, but also how to interact with cells in neighboring compartments. Third, interaction between cells in adjacent compartments initiates new morphogen gradients, gradients that orgaOver the last 20 years, the essential mechanisms of development have become clearer, mainly because nize the pattern. These gradients are initiated in a logically simple way: initially one compartment makes a modern molecular genetics has transformed traditional embryology. The longest dispute in embryology has short-range inducer (Basler and Struhl, 1994; Capdevila and Guerrero, 1994; Tabata and Kornberg, 1994), a sigbeen resolved: we now know that the adult is not preformed in the fertilized egg and that animals arise by nal to which cells of a neighboring compartment are sensitive. Those cells in range are then stimulated and step-by-step elaboration from simple beginnings, that is, by epigenesis. Much of this knowledge has come become a source of a long-range morphogen that carries positional information to the cells of both neighfrom ingenious experiments on invertebrates such as Drosophila and the nematode, Caenorhabditis elegans. boring compartments (Zecca et al., 1995; Nellen et al., 1996). We summarize each of the first two steps and Nevertheless, because so much of the genetic machinery is shared, many of the principles uncovered may then discuss the third step in more detail, taking the Drosophila wing disc as an example. We consider propapply, with variations, to all multicellular animals. Here, we describe a simple and beautiful mechanism erties of morphogen gradients in general, as they are central to the model. that is used to build pattern in the development of flies. Like the Central Dogma in molecular biology, the heart of the matter is not so much the individual molecules The Three Steps (1) The Definition of Sets of Cells involved, but more the flow of information and the logic of the system they participate in. With this proviso, it At gastrulation, the Drosophila embryo consists of about 6000 cells that are assigned to a series of precisely becomes reasonable to ask whether pattern formation in other animals uses all or some of the same logical defined primordia. By “precise,” we do not mean that the number of cells in each primordium is fixed—it is steps; and does it use similar molecules? Although this review is mainly about flies, we do approach these questhe number and arrangement of the primordia and, also, the regions of the larva and adult that they generate tions, briefly, with respect to vertebrates. Our aim is not to provide a specialized review of the fly work—this has that is invariant and precise. The cells are allocated according to their positions with respect to both the already been done well (for example, see Cohen, 1993; Blair, 1995)—but to emphasize mechanisms and princidorsoventral and the anteroposterior axes and not because they descend from particular ancestors. In both ples, to simplify, even to oversimplify, and to introduce some new hypotheses. axes, this is achieved by morphogen gradients, each