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AXIN1 and AXIN2 regulate the WNT-signaling landscape to promote distinct mesoderm programs
Rocío Hernández-Martínez1, Sonja Nowotschin1, Luke T G Harland2
1Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Developmental Cell
|July 1, 2026
Summary
WNT signaling, regulated by AXIN, guides mesoderm identity during gastrulation. It initiates differentiation and refines posterior/anterior identities, preventing premature cell fate changes.
Area of Science:
- Developmental Biology
- Cell Fate Specification
- Molecular Signaling Pathways
Background:
- Gastrulation involves specifying distinct cell lineages from pluripotent epiblast cells.
- The WNT/β-catenin pathway plays a crucial role in early embryonic development.
- AXIN proteins are known negative regulators of WNT signaling.
Purpose of the Study:
- To investigate the role of AXIN in regulating WNT signaling during gastrulation.
- To uncover previously unrecognized functions of WNT signaling in mesoderm identity specification.
- To elucidate the mechanisms by which WNT signaling differentiates posterior and anterior mesoderm identities.
Main Methods:
- Analysis of Axin1;Axin2 mutant mouse embryos.
- Single-cell and single-embryo transcriptomics.
- In vitro pluripotent stem cell differentiation assays.
Main Results:
- WNT signaling initiates primitive streak cell differentiation into mesoderm progenitors.
- WNT signaling cooperates with BMP and NODAL pathways to specify posterior and anterior mesoderm identities, respectively.
- AXIN1 and AXIN2 prevent premature differentiation of epiblast cells by regulating WNT signaling levels.
Conclusions:
- WNT signaling is critical for both initiating mesoderm differentiation and specifying distinct mesoderm lineages.
- AXIN proteins act as crucial regulators, ensuring appropriate spatiotemporal control of WNT signaling during gastrulation.
- This study reveals a novel two-layered regulatory mechanism for mesoderm specification.
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