Abelson kinase modulates epithelial cell adhesion, polarity and morphogenesis. E. Grevengoed 1, T. Jesse 2, J. Loureiro 3, M. Peifer 1,2,3,. 1) Curriculum in Genetics and Molecular Biololgy; 2) Lineberger Cancer Center; 3) Department of Biology,University of North Carolina-Chapel Hill.
Epithelial cell adhesion is initiated and maintained by adherens junctions. Proper regulation of cell-cell adhesion is essential for morphogenesis. Armadillo (Arm)/ B-catenin is a major component of adherens junctions, helping link junctions with the actin cytoskeleton. Arm is highly phosphorylated, providing one possible mode of regulation. Abelson (Abl), a non-receptor tyrosine kinase, and Enabled (Ena), a member of the Ena/VASP family, have been implicated as components of a signal transduction pathway that modulates the actin cytoskeleton during nervous system development in Drosophila. We hypothesized that these proteins might also regulate actin dynamics at adherens junctions. We identified interactions between Abl and Ena and adherens junction components by genetic and cell biological assays. Mutations in ena enhance arm defects during dorsal closure, a process that involves active cell migration and rearrangement. Ena also colocalizes with Arm at adherens junction, consistent with it modulating actin activity there. We previously identified genetic interactions between arm and abl. Mutations in abl also enhance mutations in the cadherin shotgun. Finally, we observed that embryos that are null for both maternal and zygotic Abl show defects in the development of epithelial tissues. During cellularization abl null embryos exhibit altered cell polarity and have a disrupted actin network that results in multinucleate cells. During later development, abl mutants have reduced levels of Arm in adherens junctions, cells lose their uniformity in shape and size, and germ band retraction and dorsal closure are defective. These data suggest that Abl, Ena and Arm may work together during Drosophila epithelial development, modulating cell polarity and the actin cytoskeleton at adherens junctions.