Axin1 and Axin2 regulate the WNT-signaling landscape to promote distinct mesoderm programs-Reference-Cited by-同舟云学术

Axin1 and Axin2 regulate the WNT-signaling landscape to promote distinct mesoderm programs

Published:2024-09-11 Issue: Volume: Page:
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Hernández-Martínez Rocío,Nowotschin Sonja,Harland Luke T.G.,Kuo Ying-Yi,Theeuwes Bart,Göttgens Berthold^ORCID,Lacy Elizabeth,Hadjantonakis Anna-Katerina,Anderson Kathryn V.

Abstract

ABSTRACTHow distinct mesodermal lineages – extraembryonic, lateral, intermediate, paraxial and axial – are specified from pluripotent epiblast during gastrulation is a longstanding open question. By investigating AXIN, a negative regulator of the WNT/β-catenin pathway, we have uncovered new roles for WNT signaling in the determination of mesodermal fates. We undertook complementary approaches to dissect the role of WNT signaling that augmented a detailed analysis ofAxin1;Axin2mutant mouse embryos, including single-cell and single-embryo transcriptomics, within vitropluripotent Epiblast-Like Cell differentiation assays. This strategy allowed us to reveal two layers of regulation. First, WNT initiates differentiation of primitive streak cells into mesoderm progenitors, and thereafter, WNT amplifies and cooperates with BMP/pSMAD1/5/9 or NODAL/pSMAD2/3 to propel differentiating mesoderm progenitors into either posterior streak derivatives or anterior streak derivatives, respectively. We propose thatAxin1andAxin2prevent aberrant differentiation of pluripotent epiblast cells into mesoderm by spatially and temporally regulating WNT signaling levels.

Publisher

Cold Spring Harbor Laboratory

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