Notch activity induces Nodal expression and mediates the establishment of left-right asymmetry in vertebrate embryos

Left-sided expression of Nodal in the lateral plate mesoderm is a conserved feature necessary for the establishment of normal left-right asymmetry during vertebrate embryogenesis. By using gain- and loss-of-function experiments in zebrafish and mouse, we show that the activity of the Notch pathway is necessary and sufficient for Nodal expression around the node, and for proper left-right determination. We identify Notch-responsive elements in the Nodal promoter, and unveil a direct relationship between Notch activity and Nodal expression around the node. Our findings provide evidence for a mechanism involving Notch activity that translates an initial symmetry-breaking event into asymmetric gene expression.