Misregulation of cadherin-mediated adhesion underlies numerous developmental defects and is a major contributing factor to tumor metastasis. Determining how cadherin-mediated adhesions are regulated is essential for understanding development and will aid in the design of more effective therapies to treat and prevent tumor metastasis. Morphogenesis in C. elegans provides an excellent model system in which to examine the regulation of cadherin-mediated adhesions in vivo. A cadherin-catenin complex is important for the formation of cell-cell adhesions during the process of epithelial morphogenesis, which involves movement and sealing of epidermal cells to surround the embryo in a continuous layer of epidermis [1-3]. Recent studies demonstrate that the C. elegans homologue of p120 catenin, jac-1, also plays a role in this process [4]. p120 catenin has an important yet poorly understood role in mediating cell-cell adhesion and protrusion [5-12]. Little is understood about the role of p120 catenin in vivo; however, abnormal expression of p120 catenin has been linked to aggressive tumor phenotypes [13-19]. The goal of this research proposal is to investigate the role of p120 catenin in vivo through examining the cellular and molecular mechanisms through which JAC-1/p120 catenin regulates cadherin-mediated adhesion during epithelial morphogenesis in C. elegans. This will be accomplished through a combination of genetics, 4D microscopy and RNA interference.
| Cox-Paulson, Elisabeth A; Walck-Shannon, Elise; Lynch, Allison M et al. (2012) Tropomodulin protects ?-catenin-dependent junctional-actin networks under stress during epithelial morphogenesis. Curr Biol 22:1500-5 |
| Lynch, Allison M; Grana, Theresa; Cox-Paulson, Elisabeth et al. (2012) A genome-wide functional screen shows MAGI-1 is an L1CAM-dependent stabilizer of apical junctions in C. elegans. Curr Biol 22:1891-9 |
