Fig. 13.

Model for origin and role of the AVE in anteroposterior pattering in the mouse. (a) In the peri-implantation blastocyst (E5.0), a subpopulation of primitive endoderm (PE) expressing Lefty1 and Cerl arise stochastically positioned asymmetrically in the distal egg cylinder. This population requires Nodal and Tdgf1 in the epiblast and is inhibited by Bmp4 in the extraembryonic ectoderm. (b) As the conceptus grows after implantation (E5.25), the AVE begins to also express Wnt antagonists and is repelled by Nodal and Wnt signals; the action of BMP is limited to the proximal epiblast and PE, allowing migration of AVE in the distal region. (c) As AVE migration proceeds, a second set of Lefty1; Cerl-expressing cells is induced in the distal VE (2°AVE) by Tdgf1-independent Nodal signaling. These cells and the 1°AVE migrate in a coherent stream toward the presumptive anterior, inhibiting Nodal and Wnt signaling in the epiblast and specifying the anterior neuroectoderm. Progressive loss of Nodal from the anterior limits activity to the posterior, where Nodal and Wnt maintain and amplify each other’s expression through BMP4, inducing the primitive steak (PS) in the prospective posterior. ParE parietal endoderm, PE/VE primitive/visceral endoderm, ExE extra-embryonic ectoderm. Images were modified and adapted from: Bedzhov I, Graham SJL, Leung CY, Zernicka-Goetz M (2014) Developmental plasticity, cell fate specification and morphogenesis in the early mouse embryo. Philosophical Transactions of the Royal Society B: Biological Sciences 369:20130538. doi:10.1098/rstb.2013.0538 under the terms of the Creative Commons Attribution License CC BY 3.0