The development of the small soil nematode Caenorhabditis elegans involves a rigidly determined and precisely known pattern of cell divisions. We hope to elucidate the cellular and genetic mechanisms that control this pattern of cell divisions as well as subsequent cell fate in C. elegans. We will attempt to establish the relative roles of cell autonomous and cell interactive factors, and the ways in which these factors act. We also hope to reveal aspects of the underlying genetic program that specifies cell lineage and cell fate. Our proposed studies combine physical and genetical ablation techniques to explore cell-cell interactions (how does elimination of one cell influence the fate of another?) and detailed genetical, and in some instances biochemical, studies to determine the roles of particular genes in development. One major approach will be the isolation and characterization of mutants should help establish the relationship between lineage history and cell fate, as well as reveal the specificity with which given genes influence particular cell divisions. To explore the complexity of the genetic program controlling cell division patterns, we will identify all genes that affect a specific set of cell divisions, those involved in the development of the vulva. For a limited number of genes, we hope to determine, ultimately at the molecular level, both the normal function of the gene and the ways in which mutations alter or disrupt that function. In addition, we will examine the possibility that programmed cell death provides a mechanism for controlling cell division. We will also seek interspecific cell lineage differences (as we have already found between C. elegans and another nematode, Panagrellus redivivus) and attempt to determine the genetic bases of these differences.
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