Caenorhabditis elegans body-wall muscle cell development is an advantageous system for the study of integrin signal transduction in vivo. Mutations in the
pat-2 and
pat-3 genes, which code for integrin alpha and beta subunits, respectively, severely disrupt early cytoskeletal assembly events that occur at the muscle cell membrane. The mutant embryos arrest development with the Pat phenotype ( P aralyzed, A rrested-elongation at T wo-fold), characterized by non-functional body wall muscle cells. The
pat-2 and
pat-3 genes were identified in a previously reported genome-wide screen for mutants with the Pat phenotype (Williams and Waterston, 1994). We have recently shown that a third gene identified in this screen,
pat-4, codes for the C. elegans homologue of Integrin-Linked Kinase, a serine-threonine kinase implicated in integrin-mediated signal transduction (see abstract by Mackinnon and Williams). With the goal of identifying other proteins involved in the integrin-mediated events of muscle cell development, we are pursuing the positional cloning of the
pat-6 and
pat-12 genes, which were also defined in our original screen for Pat mutants.
pat-6 maps genetically to the right end of chromosome IV. We are attempting to molecularly isolate
pat-6 by transformation rescue and are currently injecting pools of cosmid DNA from the corresponding region of the physical map. We are taking a similar approach with
pat-12. We will present our progress at the meeting. We will also present additional characterization of the muscle assembly defects in
pat-6 and
pat-12 mutants as revealed by immunostaining experiments with an existing panel of antibodies to many different muscle cell proteins.