The lin-12 gene of the nematode Caenorhabditis elegans controls particular binary decisions between alternative cell fates during development. The locus has been cloned; the protein product predicted from the partial DNA sequence includes multiple copies of a peptide motif which is homologous to a set of mammalian proteins that includes epidermal growth factor (EGF). The goal is to understand how, at the molecular level, lin-12 specifies cell fates. The work proposed herein is designed to provide basic molecular information about the structure and expression of the lin-12 gene, the structure and distribution of the lin-12 product(s), and what happens to these parameters in mutants. Standard techniques and strategies of molecular biology will be used to provide this information. The information is essential for the formulation of concise and testable models for how lin-12 specifies cell fates. Also proposed are genetic and developmental studies. Studies of lin-12 mutants will provide further information about the roles of lin-12 during nematode development. Screens for genes that interact with or are related to lin-12 might identify other components that are involved in the specification of cell fates by lin-12. The potential health relatedness of the proposed work is two-fold. First, research on the development of simpler animals such as C elegans will provide information about the fundamental processes that are involved in the development of all animals, including Homo sapiens. The specific problem - the specification of cell fate under investigation here is particularly relevant to health because disease (e.g. cancer) may result from the expression of inappropriate traits by cells. Second, the relatedness of lin-12 and the EGF set of mammalian proteins offers the possibility that an understanding of lin-12 will provide clues to the function of the common peptide motif and perhaps to hitherto unsuspected roles of growth factors in normal mammalian development.
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