Regulating Adherens Junctions and the Cytoskeleton During Morphogenesis. D. Fox, E. Grevengoed, S. Myster, G. Bain, M. Peifer. Dept Biol, Univ North Carolina, Chapel Hill, NC.

   During animal development, cells must coordinate changes in shape and position. This process of morphogenesis requires cell-cell and cell matrix junctions and the actin cytoskeleton. In epithelial cells, the major sites of cell-cell contact are adherens junctions (AJs), a protein complex that links the cytoskeleton of adjacent cells. While the key AJ components are known, the regulators of AJ assembly and connection to actin are poorly understood. Recently, we have focused on the roles of 3 candidate AJ regulators.
   One potential regulator, the kinase Abelson (Abl), is required for stable AJ assembly during embryogenesis. By examining blastoderm stage abl null embryos, we found that Abl controls the balance of actin regulators (e.g. Enabled, Ena), particularly in the apical region of the cell where AJ proteins localize. However, as these stages of development do not require AJ function, we are now focusing on Abl function during the AJ-dependent processes of embryonic morphogenesis. We are using the cold-sensitivity of abl mutants to evaluate the full requirement of Abl at these stages and to elucidate its mechanism of action. In parallel, we are examining Abl localization during embryogenesis to identify where Abl kinase may be active.
   We have also investigated the role of two proteins known to regulate AJs in cultured cells: the catenin p120 and the GTPase Rho. In flies, we found both p120 and Rho1 mutations to genetically interact with mutations in shotgun, which encodes Drosophila E-cadherin. Currently, we are investigating how these proteins regulate AJs during embryonic morphogenesis. Additionally, we are testing the hypothesis that p120 inhibits Rho. These studies will help clarify how Rho regulates AJs in vivo and address whether this regulation is dependent on p120.