Cell movements are critical features of the development of all multicellular organisms, and loss of regulation of regulation of cell movement is an essential step in cancer metastasis. While some progress has been made in identifying cell and substrate adhesion proteins required for some cell movements, how the proteins mediate movement and how the timing of such movements is regulated remains unknown. This proposal focuses on the dramatic migration of six to ten """"""""border cells"""""""" during Drosophila oogenesis as a model system for a genetic dissection of developmentally regulated cell movement. It deals primarily with one gene, slow border cells (slbo), whose function is required for initiation of migration at the proper time. Hypomorphic mutations at this locus cause delayed border cell migration, while stronger alleles cause failure of the migration, suggesting that a threshold level of slbo+ product is required to initiate the migration. A molecular characterization of this gene is proposed, including cloning the locus using existing single P-element insertion alleles, deriving a transcript map for the region, rescuing the mutant phenotype by germline transformation of slbo+ into a mutant background, and determining the deduced amino acid sequence of the slbo product. New alleles will be generated both by excision of transposons currently inserted in the gene and by EMS mutagenesis. DNA sequencing of point mutants will provide structure/function information, and production of antibodies to the protein will allow its subcellular localization and developmental distribution to be determined. Finally, genetic screens are proposed to identify other loci whose products are required for this migration and/or interact with the slbo product.
