A RhoGEF that Promotes Par6-aPKC Pathway Activity for Establishing Epithelial Polarity in Drosophila

Apical-basal polarity is important for the integrity of Drosophila embryonic epithelia. Polarity is established when Cdc42, a Rho GTPase, activates the conserved Par6/atypical protein kinase C (aPKC) complex, and recruits them to the apical domain. However, the RhoGEF that activates Cdc42 in Drosophila is unknown. Through an shRNA screen, I isolated the RhoGEF CG10188 which when knocked down produced similar defects as aPKC mutants. Furthermore, disruption of CG10188 and aPKC together enhanced the defects observed with either single disruption, demonstrating a genetic interaction between the two. However, aPKC localization appears to be independent of CG10188 regulation. Lastly, mammalian proteins that share high sequence identity with CG10188 have been previously shown to activate RhoA, another Rho GTPase, suggesting that CG10188 could be upstream of either Cdc42-Par6-aPKC or Drosophila RhoA (Rho1). Overall, my results suggest that CG10188 is a novel polarity regulator that promotes epithelial development in the Drosophila embryo.M.Sc.2017-12-01 00:00:0