Cdc42 promotes epithelial morphogenesis by coupling Par-complex and Crumbs recruitment via Par6-aPKC

Epithelial morphogenesis depends on Cdc42, which acts in part through the Par-complex (Baz/Par3-Par6-aPKC), and Crumbs (Crb/CRB3). However, how these proteins come together and interact during morphogenesis is not well understood. Here, we show that in Drosophila cells, Cdc42 is active at the apical membrane and cell-cell contacts, and couples apical recruitment of Par6-aPKC and Crb to promote apical identify. This coupling depends on Cdc42 and aPKC binding to Par6, and is mediated by Par6 binding to Crb. Conversely, Crb promotes the apical retention of Par6-aPKC, and thus Cdc42-Par6-aPKC and Crb promote each other s apical accumulation to specify the apical membrane and Zonula Adherens (ZA). Altogether, our work shows that epithelial morphogenesis relies on a two tiered-mechanism whereby Cdc42 coordinates Par-complex assembly and apical recruitment of Crb through Par6.