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Comments on Stephen Von Stetina et al. (2008) Development & Evolution Meeting "Epithelia in Search of a Good Pun" (0)
Overview
Stephen Von Stetina, & Susan Mango (2008). Epithelia in Search of a Good Pun presented in Development & Evolution Meeting. Unpublished information; cite only with author permission.
How are polarized epithelia established and maintained? This question is of critical importance, as the loss of epithelial polarity is associated with metastasis(1). There are many well-studied protein complexes that lie in specific membrane compartments with roles integral to the epithelial cell. The E-cadherin-containing adherens junction serves to link neighboring epithelial cells together while the more basal tight junction functions to separate the apical and basolateral surfaces. For some cells, E-cadherin is the major initiator of cell polarity and epithelium formation via cell-cell adhesion(2). However, recent studies have discovered E-cadherin independent polarity pathways(3-6). C. elegans offers a powerful system to study this cadherin-independent mechanism, as E-cadherin is dispensible for the initiation of epithelial polarity in nematodes(4). We study cadherin-independent epithelium formation during pharynx development. Nine pharyngeal arcade cells undergo a mesenchymal-to-epithelial transition to link the pharynx to the outer epidermis(7). Ablation of the arcade cells results in a Pharynx unattached (Pun) phenotype, in which the pharynx fails to connect to the epidermis(7). Pun animals die as they are unable to eat. Our lab has undertaken a genetic screen for Pun mutants that fail to form the arcade cell epithelium (M. Portereiko and S. Mango, unpublished). This screen revealed that loss of the central-spindlin components ZEN-4/MKLP1 or CYK-4/RhoGAP induce a Pun phenotype because the arcade cells fail to polarize(8). We speculate that CYK-4 contributes to cellular polarity via actin organization, similar to its role in the early embryo(9). We are currently studying where and when ZEN-4 and CYK-4 are needed for arcade cell polarization. In addition, we are in the process of cloning several mutants that were isolated in the Pun mutagenesis screen.