[
Adv Genet,
1990]
As recognized by T. H. Morgan, the problems of genetics and development are interwoven. Morgan noted that understanding how the genotype of an organism specifies its phenotype would require knowing the fundamental mechanisms of gene action, how genes interact to specify the properties of cells, and how cells interact to specify each adult character. We now have a basic understanding of the primary effects of genes (to encode protein or RNA products). However, little is known about how the genes of a zygote specify a complex pattern of cell divisions, the generation of diverse cell types, and the arrangement of those cells into specific morphological structures. A "favorable material" (as Morgan put it) for investigating these problems would be a simple organism in which development could be analyzed at the level of single genes and single cells. The small free-living soil nematode Caenorhabditis elegans is such an organism...
[
Annual Review of Genetics,
1984]
As recognized by T. H. Morgan, the problems of genetics and development are interwoven: understanding how the genotype of an organism specifies its phenotype requires knowing the fundamental mechanism of gene action, how genes interact to specify the properties of cells, and how cells interact to specify each adult character. We now know that the primary effect of a gene is to encode a protein or RNA product. However, little is known about how the genes of a zygote specify a complex pattern of cell divisions, the generation of diverse cell types, and the arrangement of those cells into specific morphological structures. A "favorable material" (as Morgan put it) for investigating these problems would be a simple organism in which development could be analyzed at the level of single genes and single cells. The small free-living soil nematode Caenorhabditis elegans is such an organism. C. elegans is easily grown and handled in the laboratory and is well suited for both genetic and developmental studies. This nematode consists of only about 1,000 (non-germ) cells, and both its anatomy and its development are essentially invariant. The complete anatomy of C. elegans, including the "wiring diagram" of the nervous system, is known at an ultrastructural level. In addition, the developmental origin of every cell is known since the complete cell lineage from the zygote to the adult has been determined. The genetic properties of C. elegans allow researchers to combine the classical Mendelian approach of Morgan and his coworkers with the approach of modern microbial genetics: C. elegans is diploid but microscopic in size (so large numbers of animals can be handled, up to 10*5 on a single petri dish) and has a very rapid life cycle (an egg matures into a fertile adult within two to four days, depending upon temperature; this adult produces 300-400 progeny over the next few days, resulting in an effective organismal doubling time of about 15 hours). Many aspects of the biology of C. elegans have been reviewed. Here we describe how these features have led to an initial understanding of some of the issues concerning genetics and development that Morgan raised fifty years ago. We review the methods underlying and the results derived form four approaches that have been used to study the genetics of nematode development. The first approach, which takes advantage of the genetic diversity generated by evolution, is to compare the development of related species. For example, simple differences in otherwise identical cell lineages may be the result of one or a few mutational events that occurred during the divergence of two species; the nature of these differences can suggest ways in which genes may control development. The second approach is to identify a large set of mutations that affect particular cell lineages; this approach can indicate the number, types, and specificities of genes that affect particular developmental events. The third approach involves the detailed genetic analyses of genes identified by mutations that alter development; such studies can reveal the wild-type functions of those genes and thereby identify genes that play regulatory roles in development. The fourth approach is to examine the interactions among mutations using studies of extragenic suppression and epistasis; this type of analysis can suggest how genes interact during normal development to