Kuo-Chen Jung | 2009-2011
M.S. in Biology, May 2012
How does Canoe regulate morphogenesis?
During Drosophila embryogenesis, cells divide, change cell shape, and migrate while remaining attached to each other to maintain embryo integrity. However, how embryos coordinate cell movement and cell adhesion is still largely unknown. Canoe (Cno) is a linker between adhesive junctions and the actin cytoskeleton and thus may act as a regulator during this process. In our lab, we take advantage of strong genetic and cell biological tools in Drosophila as a model. Previous work by Jessica Sawyer and Nathan Harris in our lab revealed that Cno is essential for apical constriction of the mesoderm cells and is regulated by Rap1 GTPase. I am further characterizing how Rap1 regulates Cno activity, and what role Cno plays in other processes during embryogenesis such as dorsal closure.Cno and its mammalian homolog afadin also bind fly Pyd and mammalian ZO-1, respectively, and cno genetically interacts with pyd during embryonic and adult morphogenesis (Takahashi et al., 1998).
Previous work documented a role for Cno in dorsal closure and head involution (Miyamoto et al., 1995; Takahashi et al., 1998; Boettner et al., 2003). I have further characterized the role of Cno during dorsal closure, and compared its phenotypes with those of its putative partner Polychaetoid, the fly ZO-1 homolog. My analysis reveals that zygotic cno mutants do not have significant defects in the maintenance of cell-cell adhesion, and that they assemble a leading edge actin cable. However, my data suggest that the junctional attachment sof this cable or its mechanical integrity are compromised. This leads to defecst in leading edge cell shape. My data further reveal that loss of zygotic Cno leads to defects in the lcoalization of the actin regulator Enabled to the ends of the actin cable, and strong dose-sensitive genetic interactions between cno and ena are consistent with them working together in the same process. I am further examining the mechanistic role of Cno during doral closure, and also examining how it works with Rap1 during earlier development.
Publications
- Choi, W. , Jung, K.-C., Nelson, K.S., Bhat, M.A., Beitel, G.J., Peifer, M., and Fanning, A.S. (2011). The single Drosophila ZO-1 protein Polychaetoid regulates embryonic morphogenesis in coordination with Canoe/Afadin and Enabled. Molecular Biology of the Cell 22, 2010-2030.
- Sawyer, J.K., Choi, W. , Jung, K.-C., Hi, L., Harris, N.J., and Peifer, M., (2011). A contractile actomyosin network linked to adherens junctions by Canoe/afadin helps drive convergent extension. Molecular Biology of the Cell 22, 2491-508.
- Roberts,D.M., Pronobis, M.I., Alexandre, K.M., Rogers, G.C., Poulton, J.S., Schneider, D.E., Jung, K.-C., McKay, D.J., and Peifer, M. (2012). Regulation of Wnt signaling by the tumor suppressor APC does not require ability to enter the nucleus nor a particular cytoplasmic localization. PLoS One 7: e31284
