Laboratoire de Biologie du Développement, Université Pierre et Marie Curie, Sorbonne Universités, UMR CNRS 7622, 75252 Paris Cedex 05, France.
Mol Biol Cell. 2011 Aug 15;22(16):2957-69. doi: 10.1091/mbc.E11-01-0074. Epub 2011 Jun 16.
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 knockdown 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 (ECM). 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 β(1) integrins. This was associated with a decrease of cell proliferation, a disruption of multiciliated-cell intercalation, and the down-regulation of the transcription factor P63, a marker of differentiated epidermis. In addition, we demonstrated that inhibition or activation of the Notch pathway prevents and promotes transcription of X-dg. Our study showed for the first time in vivo that Dg, in addition to organizing laminin in the ECM, also acts as a key signaling component in the Notch pathway.
层粘连蛋白聚糖（Dg）是一种跨膜蛋白，参与基底膜结构的组装和维持，基底膜结构对于组织形态发生和跨膜信号转导是必需的。我们使用一种 morpholino 敲低方法研究了 Dg 在非洲爪蟾皮肤形态发生过程中的功能。Dg 的缺失通过影响多纤毛细胞的插入、层粘连蛋白的沉积以及细胞外基质（ECM）中纤维连接蛋白的组织来破坏表皮分化。Dg 的耗竭还会影响细胞-细胞黏附，这表现为细胞间接触处 E-钙黏蛋白表达减少，而β1 整合素的分布不受影响。这与细胞增殖减少、多纤毛细胞插入中断以及转录因子 P63 的下调有关，P63 是分化表皮的标志物。此外，我们证明 Notch 途径的抑制或激活可以阻止和促进 X-dg 的转录。我们的研究首次在体内证明，Dg 除了在 ECM 中组织层粘连蛋白外，还作为 Notch 途径中的关键信号成分发挥作用。
