Role of Caenorhabditis elegans lin-40, synMuv, and nhr-25 genes in regulating cell fate specification and asymmetric cell division during vulval development

Vulval development in C. elegans involves many fundamental cellular events, including cell division, cell migration, and cell fusion. This thesis research focuses on understanding functions of the lin-40 and synMuv genes in controlling vulval fate specification and activities of lin-40 and nhr-25 in regulating cell-type specific division patterns during vulval morphogenesis.; Genetic analyses of lin-40 reveal that it negatively regulates vulval fate specification, as mutations in lin-40 led to extra cells adopting the vulval fate. lin-40 codes for a homologue of the MTA (metastasis-associated factor) proteins in mammals. Given that MTAs were identified as components of the NuRD (nucleosome remodeling and histone deacetylation) complex, and that other NuRD complex components in C. elegans seem to function together with Rb/E2F to repress the vulval fate in the class B synMuv (synthetic Multivulva) pathway, it is possible that lin-40 acts collaboratively with these genes during vulval development. However, my genetic study did not identify the typical synthetic interaction between lin-40 and any synMuv genes. Instead, I have evidence that lin-40 functions independently of the synMuv genes and regulates a lin-39-mediated cell fusion process that affects the potential of vulval precursor cells to adopt the vulval fate. In addition, my study suggests that lin-40 regulates vulval cell division and its function might be required for imposing a cell cycle delay in some vulval cells to prevent longitudinal division and therefore allow transverse division to occur.; nhr-25 encodes a transcription factor similar to the nuclear hormone receptors, and it belongs to a subfamily of the orphan receptors. A mutation that disrupts the DNA-binding activity of NHR-25 resulted in abnormalities in the asymmetric division, fusion and migration of vulva] cells, suggesting that nhr-25 function is involved in controlling many aspects of vulval development. Interestingly, in the nhr-25( ku217) mutant, the transverse division of vulval cells was specifically blocked, whereas cell division along the longitudinal axis was not affected. Therefore, nhr-25 activity is essential for vulval cells that normally divide transversely to adopt the normal cell fate and my data suggest that this activity is required before and/or during the final round of vulval cell division.