Nodal signaling from the visceral endoderm is required to maintain Nodal gene expression in the epiblast and drive DVE/AVE migration

In the early mouse embryo, a specialized population of extraembryonic visceral endoderm (VE) cells called the anterior VE (AVE) establishes the anterior posterior (AP) axis by restricting gastrulation-inducing signals to the opposite pole. These cells arise at the distal tip of the egg cylinder stage embryo and then asymmetrically migrate to the prospective anterior following the path of an earlier arising and migrating population called the distal VE (DVE). The Nodal-signaling pathway has been shown to have a critical role in the generation of the DVE and AVE and in their migration. The Nodal gene is expressed in both the VE and in the pluripotent epiblast, which gives rise to the germ layers. Previous findings have provided conflicting evidence as to the relative importance of Nodal signaling from the epiblast vs. VE for AP patterning. Here we show that conditional mutagenesis of the Nodal gene specifically within the VE leads to reduced Nodal expression levels in the epiblast and incomplete or failed AVE migration. These results support a required role for VE Nodal to maintain normal levels of expression in the epiblast, and suggest signaling from both VE and epiblast is important for AVE migration.