Present address: Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10065, USA.
Department of Medicine, Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA Present address: Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10065, USA.
Biol Open. 2014 Jun 13;3(7):583-90. doi: 10.1242/bio.20148243.
The node and notochord (and their equivalents in other species) are essential signaling centers, positioned along the plane of bilateral symmetry in developing vertebrate embryos. However, genes and mechanisms regulating morphogenesis of these structures and their placement along the embryonic midline are not well understood. In this work, we provide the first evidence that the position of the node and the notochord along the bilateral plane of symmetry are under genetic control and are regulated by integrin α5β1 and fibronectin in mice. We found that the shape of the node is often inverted in integrin α5-null and fibronectin-null mutants, and that the positioning of node and the notochord is often skewed away from the perceived plane of embryonic bilateral of symmetry. Our studies also show that the shape and position of the notochord are dependent on the shape and embryonic placement of the node. Our studies suggest that fibronectin regulates the shape of the node by affecting apico-basal polarity of the nodal cells. Taken together, our data indicate that cell-extracellular matrix interactions mediated by integrin α5β1 and fibronectin regulate the geometry of the node as well as the placement of the node and notochord along the plane of bilateral symmetry in the mammalian embryo.
节点和脊索(及其在其他物种中的对应物)是沿着脊椎动物胚胎的双侧对称面定位的重要信号中心。然而,调节这些结构的形态发生及其在胚胎中线上的位置的基因和机制尚不清楚。在这项工作中,我们首次提供证据表明,节点和脊索在双侧对称面中的位置受遗传控制,并受整合素 α5β1 和纤连蛋白在小鼠中的调节。我们发现,整合素 α5 缺失和纤连蛋白缺失突变体中的节点形状常常反转,并且节点和脊索的定位常常偏离胚胎双侧对称面的感知平面。我们的研究还表明,脊索的形状和位置取决于节点的形状和胚胎位置。我们的研究表明,纤连蛋白通过影响节点细胞的顶底极性来调节节点的形状。总之,我们的数据表明,整合素 α5β1 和纤连蛋白介导的细胞-细胞外基质相互作用调节节点的几何形状以及节点和脊索在哺乳动物胚胎双侧对称面中的位置。