Dlg5 maintains apical aPKC and regulates progenitor differentiation during lung morphogenesis

Cell polarity plays an important role in tissue morphogenesis; however, the mechanisms of polarity and their role in mammalian development are still poorly understood. We show here that membrane-associated guanylate kinase protein Dlg5 is required for proper branching morphogenesis and progenitor differentiation in mammalian lung. We found that during lung development Dlg5 functions as an apical–basal polarity protein, which is necessary for the apical maintenance of atypical protein kinase C (aPKC). These results identify Dlg5 as a regulator of apical polarity complexes and uncover the critical function of Dlg5 in branching morphogenesis and differentiation of lung progenitor cells.

► Dlg5 is necessary for lung branching morphogenesis.
► Dlg5 is required for proper differentiation of distal lung progenitor cells.
► Loss of the apical–basal cell polarity of epithelial progenitors is one of the primary defects in Dlg5−/− lungs.
► Dlg5 is necessary for the apical membrane domain maintenance of aPKC.