Abelson kinase regulates the apical actin cytoskeleton. E.E. Grevengoed , M. Peifer. Dept Biol, UNC, Chapel Hill, NC.
We previously identified a role for the non-receptor tyrosine kinase Abelson (Abl) during epithelial morphogenesis. Maternal/zygotic ablmutants (ablMZ) die during embryogenesis and exhibit defects during germ band retraction and dorsal closure. Our data suggested that in the absence of Abl, adherens junction stability is altered. It remained unclear, however, if Abl directly affects junctions or acts more indirectly by affecting the actin cytoskeleton. We have extended this work and found that ablMZ mutants also have defects during both nuclear divisions 10-13 as well as cellularization. ablMZ mutants fail to properly localize actin to both metaphase and cellularization furrows, resulting in multinucleate cells. Using moesin GFP to follow actin dynamics, we imaged live embryos and can visualize both the mechanical failure of metaphase furrows and the incomplete formation of cellularization furrows in ablMZ mutants. Enabled (Ena), a known Abl substrate, plays a role in modulating actin dynamics. In ablMZ mutants, Ena levels are increased specifically along the apical cortex of the embryo. Recent data in fibroblasts suggested that Ena prohibits branching of microfilaments, encouraging their elongation at the leading edge. We hypothesized that elevated levels of Ena along the apical cortex in the ablMZ mutants alter the cytoskeleton there. During wild type cellularization, microvilli are present above each nucleus. As cellularization progresses these microvilli diminish, leaving the surface of each cell relatively smooth upon gastrulation. In the ablMZ mutant embryos, however, using SEM we find that these microvilli fail to diminish and instead continue to elongate throughout cellularization. These data suggest that Abl regulates apical actin dynamics, acting through Ena to ensure the sort of actin polymerization required to properly execute furrow formation. We are currently looking for interactions between Abl and other actin regulators important during syncytial developmental such as Arp2/3 and Diaphanous, which may further our understanding of actin regulation during development.