We are addressing the general problem of how patterns form within fields of cells by studying antero-posterior pattern formation in C. elegans. Our entry point has been the gene mab-5, which we showed to be a homeotic gene required for ectodermal and mesodermal cells located in a posterior body region to undergo position-specific migrations, divisions and differentiations. We are now trying to learn how mab-5 activity is targeted to posterior cells, and to understand how mab-5 controls cell differentiation. During the current funding period, we have found that mab-5 RNA is localized in the posterior body region, which implies that at least one mechanism that positions mab-5 activity acts at the level of mab-5 RNA. We have identified a number of genes that may influence this localization. In particular, we have found that a regulated system of local cell-cell interactions positions mab-5 function in laterally located cells. In addition, we have found that mab-5 contains a homeobox closely related to those of Drosophila homeotic genes within the bithorax and Antennapedia complexes. This finding suggests that mab-5 regulates transcription and that there may be an underlying similarity between this pattern forming system and that of Drosophila. We now plan to utilize the information and molecular probes obtained in the current funding period to study mechanisms of mab-5 localization and function with much greater depth and resolution than was possible previously. We plan to determine exactly which cells express mab-5 during development, to learn what types of position-specific, cell-specific and sex-specific regulation ?nab-5 is subject to. We will localize cis-acting regulatory regions required for specific modes of regulation, and identify and analyze genes that may encode transacting regulatory factors. We will initiate a detailed genetic and molecular study of the local cell interactions that regulate mab-5 expression. We will analyze genes in C. elegans we, have identified that are homologous to Drosophila patterning genes, to determine whether additional similarities exist between these two regulatory systems. Finally, we will determine whether mab-5 activity is sufficient to cause anterior cells to adopt posteror-specific fates, and we will begin to identify genes that may be regulated by mab-5 to initiate specific pathways of cell differentiation.
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