Apical Complex Molecules Play Essential And Novel Roles In Collective Cell Migration

The most apparent feature of epithelia is their apical-basal polarity.In developmental and physiological context,this epithelial polarity needs to be precisely regulated,whereas mis-regulation will lead to various diseases including cancer.During collective migration,a cohesive group of cells still often maintain cell-cell junctions and apical polarity,which are the characters of epithelial cells.However,the contribution of this apical polarity to migration is still not clearly understood.Here,we use Drosophila border cells,a well-studied migratory model to analyze functions of key apical polarity molecules including Crb complex(Crb/Sdt/Patj)and Par complex(Par6-aPKC-Par3/Baz).Border cell cluster is a group of 6-8 cells.They originate from anterior follicular epithelial cells in the ovary,then penetrate into adherent nurse cells and finally migrate to the border of oocyte.We found that components of apical polarity complexes play a number of essential roles in promoting collective migration of border cells during Drosophila oogenesis.First,components of Crumbs(Crb)complex act in the apical junction and membrane to limit the protrusion of lamellipodia to lateral region of outer border cells.Second,components of Crb complex and Par complex act together to ensure distribution of two populations of aPKC in the apical junction and near the lateral membrane respectively.Interestingly,the moderate amount of aPKC near the basolateral membrane activates the downstream Rac GEF(Guanine nucleotide exchange factor),Tiaml/Sif,to promote the Rac-induced and actin-rich protrusions at the leading edge.Moreover,we found that endocytic recycling was required for the polarized distribution of these two populations of aPKC.Third,loss of Crb function or increased activity of the Par complex component,aPKC,affect the inside-outside polarity of border cellsTogether,these results demonstrate that the multiple functions of apical complex components allows them to promote apical-basal,front-back,inside-outside polarities during collective cell migration.