[
1980]
The free-living nematode Caenorhabditis elegans has attracted attention in recent years as an organism for the study of the genetic control of development. This chapter briefly describes the present state of this work. Many of the studies reported on here have not yet been published but have been described in "The Worm Breeder's Gazette", an informal newsletter I edit, and at a C. elegans meeting held at Cold Spring Harbor in May 1979. A previous review of this field was written by Riddle (1978). The use of free-living nematodes in genetic studies was first suggested by Dougherty and Calhoun in 1948. Early studies of C. elegans by Dougherty and co-workers (1959) emphasized methods of axenic cultivation while the sexual cycle was described by Nigon (1949). The present interest in C. elegans, however, was triggered by Sydney Brenner who took up the organism in the late 1960s as a possibly useful organism for the study of the genetic control of the nervous system and of behavior (Brenner, 1973). It was largely due to Brenner (1974) that the present methods of cultivation and of genetic analysis were developed.
Genetic analysis of C. elegans development has focused on developmental events that take place after hatching, during postembryonic development. After hatching with 558 cells, about 10% of these are blast cells that undergo further cell divisions (Fig. 1) to generate a total of 959 neurons, muscles, intestinal and hypodermal cells in the hermaphrodite and 1031 cells in the male. Like embryonic development (se Edgar, Chap. 19 this Vol.), the pattern of cell division and differentiation during C. elegans postembryonic development is nearly invariant and has been completely described. The cell lineage of wild-type, mutant, or laser-ablated animals can be determined by direct observation of development using Normarski optics. Because most cells during C. elegans postembryonic development generate unique patterns of descendents (though symmetries in the lineage exist), the cell lineage produced by a particular blast cell during development is a signature of that cell's identity. Any changes in cell identity, induce, for example, by laser ablation or neighboring cells or by mutation, can be recognized by a change in the lineage produced by that cell. By laser ablation, it has been shown that in many cases, that patterns of cell lineage executed by particular cells do not depend on their neighbors and instead reflect some intrinsic developmental program. On the other hand, the lineages of particular blast cells, for example, those that generate the hermaphrodite vulva, have been shown by laser ablation experiments to depend on interactions with their neighbors. Thus the pattern of cell divisions and differentiations that normally occur during C. elegans development depends on the ancestry of cells in some cases on their neighbors or positional signals in other cases. Two major goals of developmental genetic analysis in C. elegans have been to explain how genes couple cell lineage information to cell identity and to explain how genes control and mediate cell-cell interactions. As described below, this analysis has revealed molecular mechanisms for the generation of lineage asymmetry and for intercellular signaling that are general to perhaps all metazoans.