GENETIC CONTROL OF NEMATODE DEVELOPMENT

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The development of the small soil nematode Caenorhabditis elegans involves an invarient and precisely known temporal pattern or sequence of cell divisions and differentation 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-intrinsic vs cell-extrinsic functions in elaborating and interpreting temporal information during development? 4) How do these genes functionally 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 and executing a specific temporal switch in cell fate - the switch from larval programs (cell division and larval cuticle synthesis) to adult program (adult cuticle synthesis) for hypodermal "seam" cells. For each newly identified gene, and for certain of the eight previously identified genes affecting this switch, detailed genetic analysis will be applied to determine their respective null phenotypes and thus their roles in wild-type development. Functional interactions will be explored by constructing multiply-mutant strains with known genetic lesions in two or more hetero-chronic genes. Temperature shift experiments using temperature-sensitive alleles will be used to investigate the time of action of each gene. Additional mutants will be sought defective specifically in the timing of postdauer development. Genetic analysis of genes so identified will be carried out. Genes transcribed stage- specifically, and/or specifically during either postdauer or nondauer development will be identified by probing recombinant phage libraries with cDNA probes. The sequences of these genes will be used to analyze the effects of heterochronic mutations on the expression of genes involved in specific developmental programs.