HOMEOBOX GENE REGULATION IN C ELEGANS DEVELOPMENT

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In the nematode C. elegans, the specific identities of the nine sensory rays in the male tail are combinatorially controlled by homeotic-cluster (HOM-C) genes. The long-term goal of this proposal is to understand the means by which this HOM-C expression pattern is generated, with particular emphasis on one critical component, the Hox gene egl-5. Because vertebrate development employs similar strategies, this research will have relevance for understanding human development and developmental defects. A two-fold experimental approach is proposed here. First, a genetic screen will be performed to isolate animals which have defective egl-5 expression patterns. This approach is feasible because misregulation of egl-5 expression is predicted to cause specific, identifiable mutant phenotypes in the structure of the male tail. This may allow the identification and characterization of genes which act to generate HOM-C expression patterns. Concurrently, a molecular approach will be taken: using a reporter gene construct, the regulatory elements of the egl-5 gene which are necessary and sufficient for its wild-type expression pattern will be delineated. The means by which these elements function will then be studied; genes identified in the mutant screen may be candidate regulatory factors which act through these elements. This work should shed light on the generation of HOM-C gene codes, which remains an important and interesting problem in developmental biology.