Axin1 and Axin2 cooperate to instruct mesodermal fates during mouse gastrulation

By investigating Axin, a negative regulator of the WNT/b-catenin pathway, we uncover new roles for WNT signaling in the determination and segregation of extraembryonic, posterior lateral plate, and intermediate mesoderm fates. We undertook two complementary approaches to spatially and temporally dissect the role of WNT signaling at gastrulation.

We augmented detailed analysis of Axin1;Axin2 mutant mouse embryos, including single-cell and single-embryo transcriptomics, with in vitro Epiblast-Like Cell (EpiLC) differentiation assays, which allowed us to reveal how coordinated activities of the WNT/b-catenin and BMP/pSmad1/5/9 pathways activate mesoderm lineage-specific programs. Our findings lead us to propose that Axin1 and Axin2 act to prevent aberrant differentiation of epiblast cells into extraembryonic, intermediate, paraxial and axial mesoderm, by spatially and temporally regulating levels of WNT signaling.