Dystroglycan is involved in skin morphogenesis downstream of the Notch signaling pathway

Dystroglycan (Dg) is a transmembrane protein involved both in the assembly and maintenance of basement membrane structures essential for tissue morphogenesis, and the transmission of signals across the plasma membrane. We used a morpholino knock down approach to investigate the function of Dg during Xenopus laevis skin morphogenesis. The loss of Dg disrupts epidermal differentiation by affecting the intercalation of multiciliated cells, deposition of laminin and organization of fibronectin in the extracellular matrix. Depletion of Dg also affects cell-cell adhesion, as shown by the reduction of E-cadherin expression at the intercellular contacts, without affecting the distribution of β1 integrins. This was associated with a decrease of cell proliferation, a disruption of multiciliated cells intercalation and the down regulation of the transcription factor P63, a marker of differentiated epidermis. In addition, we demonstrate that inhibition or activation of the Notch pathway prevents and promotes transcription of X-dg. Our study shows for the first time in vivo, that Dg in addition to organizing laminin in the extracellular matrix also acts as a key signaling component in the Notch pathway.