Dissecting signalling hierarchies in the patterning of the mouse primitive streak using micro-patterned EpiLC colonies

Molecular embryology studies have established that the patterning of the gastrula-stage mouse embryo is dependent on a regulatory network where the WNT, BMP and NODAL signalling pathways cooperate. Still, important aspects of their respective contributions to this process remain unclear. Here, studying their impact on the spatial organization and the developmental trajectories of micro-patterned Epiblast Like Cells (EpiLC) colonies, we show that when BMP is present, it dominates NODAL and WNT and imposes a posterior character to the colonies differentiation. However, the use of two Nodal mutant cell lines allowed us to show that prior to BMP action, NODAL is required to establish the mesendodermal lineage. The fact that mutant phenotypes were more severe in vitro than in vivo suggests that embryonic phenotypes are partially rescued by ligands of extra-embryonic or maternal origin. Our work demonstrates the complementarity of micro-patterned EpiLC colonies to embryological approaches.