| Summary: | In epithelial cells, establishment of apical-basal polarity and specification of distinct membrane domains, such as cell-cell contacts, are fundamental processes during organogenesis. Polarised epithelial morphogenesis relies on a set of conserved polarity factors, namely Cdc42-Par6-aPKC-Baz/Par3 (the Par complex) and Crumbs-Stardust-Patj (the Crumbs complex). My work addresses how these two complexes cooperate in specifying and developing the apical membrane and epithelial cell contacts. Within the Par complex, Par6 is an effector of the small GTPase Cdc42 and is thought of as a regulatory unit for aPKC, which is the signalling component of the complex. My work indicates that in epithelial cells, Par6 assumes a novel and essential role in coupling cortical polarity with membrane delivery to drive epithelial morphogenesis. More specifically, Par6 binding to Cdc42 directs the assembly of the Par complex and enables the apical localisation of Par6-aPKC. In addition, Cdc42 enables apical retention of Par6-aPKC through promoting Par6 binding to Crumbs, which defines the boundaries of epithelial cell contacts. During this process, a link between the Par complex and the exocyst, couples polarity at the apical cortex with cargo delivery, including Crumbs. This coupling between Par6 and Crumbs defines a feedback loop that drives apical membrane and epithelial cell contact morphogenesis. In parallel, another Cdc42 effector, Mbt/Pak4, regulates the accumulation of junctional proteins at the cell contacts and enables a retention mechanism for Baz/Par3 that prevents ectopic Par complex assembly at the lateral cortex. Altogether, my work elucidates how two Cdc42 effectors, Par6 and Mbt, coordinate the specification and maturation of the apical membrane and cell contacts, via exocyst-dependent membrane delivery and multiple retention mechanisms.
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