[
WormBook,
2005]
The C. elegans germ line proliferates from one primordial germ cell (PGC) set aside in the early embryo to over a thousand cells in the adult. Most germline proliferation is controlled by the somatic distal tip cell, which provides a stem cell niche at the distal end of the adult gonad. The distal tip cell signals to the germ line via the Notch signaling pathway, which in turn controls a network of RNA regulators. The FBF-1 and FBF-2 RNA-binding proteins promote continued mitoses in germ cells located close to the distal tip cell, while the GLD-1 , GLD-2 , GLD-3 , and NOS-3 RNA regulators promote entry into meiosis as germ cells leave the stem cell niche. In addition to these key regulators, many other genes affect germline proliferation.
[
1983]
In 1974, Sydney Brenner published an elegant paper that described the genetic system of Caenorhabditis elegans and led to its use in research on a wide variety of topics, including aging (Brenner, 1974). Its small size (1mm as an adult) and determinate cell lineage has allowed a description of the entire somatic cell lineage from the one-cell stage to the adult (Sulston and Horvitz, 1977; Deppe et al., 1978; Kimble and Hirsh, 1979; Suslton et al., personal communication). Its ease of culture makes it an organism of choice for studies of various aspects of anatomy and physiology, including muscle formation and function (Zengel and Epstein, 1980; Mackenzie and Epstein, 1980), cuticle formation (Cox et al, 1981), neuroanatomy (Ward et al, 1975; Ware et al, 1975; Sulston et al, 1975), and behavior (Dusenbery, 1980). Several genes have been cloned by recombinant DNA techniques ablation (Kimble, 1981; Laufer and von Ehrenstin, 1981) procedures, as well as most of the modern molecular techniques, are in use.
[
Harvey Lect,
1988]
Animal development involves a complex pattern of cell divisions ultimately leading to the generation of a highly diverse complement of cell types. What are the molecular mechanisms responsible for controlling patterns of cell division and for causing cells to become different from one another? To address the problem, my colleagues and I have been examining how genes control cell lineage and cell fate in the nematode Caenorhabditis elegans. The study of C. elegans was pioneered by Sydney Brenner (1973, 1974), who selected this organism because it is highly tractable genetically (e.g., see Herman, 1988)and because it is simple and essentially invariant in its cellular anatomy (the adult hermaphrodite is now known to contain a total of 959 somatic cell nuclei; Sulston and Horvitz, 1977; Kimble and Hirsh, 1979; Sulston et al., 1983). The invariance in C. elegans anatomy reflects a similar invariance in development. For example, the cell lineage of C. elegans is essentially the same in all individuals (Sulston and Horvitz, 1977; Kimble and Hirsh, 1979; Sulston et al., 1983). This cell lineage was determined by direct observation of living nematodes: individual nuclei were watched with the aid of Nomarski optics as they migrated,
[
Methods Cell Biol,
1995]
DNA transformation assays in a whole organism provide experimental links between molecular structure and phenotype. Experiments with transgenic Caenorhabditis elegans start in general with the injection of DNA into the adult gonad. Effects on phenotype or gene expression patterns can be analyzed either in F1 progeny derived from the injected animals or in derived transgenic lines. Microinjection of C. elegans was first carried out by Kimble et al. (1982). Stinchcomb et al. (1985) then showed that injected DNA could be maintained for several generations in transgenic lines. The first selective methods for producing and maintaining transgenic lines were reported in 1986 (Fire, 1986). These methods have been considerably improved since then (Mello et al., 1991) , so that assays involving DNA transformation are now a standard part of the experimental repertoire for C. elegans.