The goal of this project is to understand the molecular basis for the establishment of a pattern of cell types in one tissue by an inductive signal from another tissue. Vulval development in the nametode Caenorhabditis elegans is a simple example of inductive pattern formation. A single cell in one tissue induces three of six precursor cells in another tissue to generate the vulva. The distance of each multipotent precursor cell from the source of the inductive signal specifies which of three cell types it becomes. Thus, a spatial pattern of cell types is established. Fifteen genes are necessary for the correct specification of this spatial pattern. The genetic properties of one such gene, let-23 indicate that it plays a key role in transduction of the inductive signal. The let- 23 locus is defined both by mutations that eliminate the response to the signal and those that cause an increased sensitivity to the signal. This study will use molecular and classical genetics to understand how the types of the precursor cells are specified by the inductive signal.
The specific aims of this proposal are (1) the identification of genes that control production of the inductive signal; (2) the molecular and genetic characterization of let-23; and (3) the identification of genes specific to particular types of vulval precursor cells. The proposed work is health-related in two ways. First, the problem of how interactions between cells specify their fates is relevant to the problem of cancer because many gene products associated with transformed cells are known to be structurally and functionally homologous to gene products that act in intercellular signalling pathways. Basic questions concerning the roles of such gene products in an intact developing organism can be addressed in an invertebrate such as C. elegans. Second, an understanding of the molecular basis for the sexual maturation of this free-living nematode may help in the development of new antihelminthic agents directed against parasitic nematodes.
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