Axin1 and Axin2 Regulate the WNT-signaling Landscape to Promote Distinct Mesoderm Programs

Overview

Journal bioRxiv

Date 2024 Sep 24

PMID 39314295

Authors

Rocio Hernandez-Martinez

Sonja Nowotschin

Luke T G Harland

Ying-Yi Kuo

Bart Theeuwes

Berthold Gottgens

Elizabeth Lacy

Anna-Katerina Hadjantonakis

Kathryn V Anderson

Affiliations

Soon will be listed here.

Abstract

How 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 of ; mutant mouse embryos, including single-cell and single-embryo transcriptomics, with pluripotent 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 that and prevent aberrant differentiation of pluripotent epiblast cells into mesoderm by spatially and temporally regulating WNT signaling levels.

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