Maria Pulina, Dong Liang, Sophie Astrof

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.