GENETIC CONTROL OF NEMATODE DEVELOPMENT

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The development of the small nematode Caenorhabditis elegans involves an invariant and precisely known temporal pattern or sequence of cell divisions and differentiation events. The long term goal of this work is to elucidate how this temporal schedule of development is genetically encoded. The general questions to be addressed are: 1) What are the roles of individual genes in controlling temporal sequences of developmental events? 2) What are the tissue- and stage-specificities of those genes? 3) What are the relative roles of genes encoding cell-extrinsic vs cell-intrinsic functions in elaborating and interpreting temporal information during development? 4) How do these genes interact among themselves and with genes controlling basic cellular processes such as cell division and differentiation? The genetic and phenotypic properties of mutants with altered temporal patterns of development ("heterochronic mutants") will be studied in detail. An attempt will be made to identify by mutation all genes involved in controlling a specific temporal switch in cell fate - the switch from larval programs (cell division and larval cuticle synthesis) to adult programs (adult cuticle synthesis) for hypodermal "seam" cells. For each newly identified gene, and for certain of the five previously identified genes affecting this switch, detailed genetic analysis will be applied to determine their respective null phenotypes and thus their wild-type developmental roles. Functional interactions will be explored by constructing multiply-mutant strains with known genetic lesions in two or more heterochronic genes. Temperature shift experiments using temperature-sensitive alleles will be used to investigate time of action of each gene. Mosaic analysis will be employed for selected genes to determine if they act cell autonomously. This work uses the nematode as a model system to study basic questions concerning the genetic control of cell divisions, differentiation and pattern formation and therefore may help deepen our understanding of the causes of genetic developmental disorders and neoplasia.