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Peer-reviewedCC BYDevelopmental Cell

AXIN1 and AXIN2 regulate the WNT-signaling landscape to promote distinct mesoderm programs

  • Rocío Hernández-Martínez1
  • Sonja Nowotschin2
  • Luke T. G. Harland3
  • Ying-Yi Kuo2
  • Bart Theeuwes4
  • Berthold Göttgens4
  • Elizabeth Lacy2
  • Anna‐Katerina Hadjantonakis5
  • Kathryn V. Anderson2
5 affiliations
  1. 1Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: [email protected]
  2. 2Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
  3. 3Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK; Department of Haematology, University of Cambridge, Cambridge CB2 0RE, UK; Wolfson College, University of Cambridge, Cambridge CB3 9BB, UK
  4. 4Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK; Department of Haematology, University of Cambridge, Cambridge CB2 0RE, UK
  5. 5Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: [email protected]
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Abstract

How distinct lineage identities are specified from pluripotent epiblast cells during gastrulation is a longstanding open question. By investigating AXIN, a negative regulator of the WNT/β-catenin pathway, we have uncovered previously unrecognized roles for WNT signaling in the specification of distinct mesoderm identities. Using complementary approaches, including a detailed analysis of Axin1;Axin2 mutant mouse embryos involving single-cell and single-embryo transcriptomics and in vitro pluripotent stem cell differentiation assays, our data revealed two critical layers of regulation. First, WNT initiates differentiation of primitive streak cells into mesoderm progenitors. Next, WNT amplifies and cooperates with bone morphogenetic protein (BMP)/pSMAD1/5/9 or NODAL/pSMAD2/3 to propel differentiating mesoderm progenitors into either posterior or anterior streak identities, respectively. We propose that Axin1 and Axin2 function to prevent precocious differentiation of pluripotent epiblast cells into mesoderm through the spatiotemporal regulation of WNT-signaling levels.

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Cite

BibTeXRIS
BibTeX
@article{hernandezmartinez2026axin1,
  title = {{AXIN1 and AXIN2 regulate the WNT-signaling landscape to promote distinct mesoderm programs}},
  author = {Rocío Hernández-Martínez and Sonja Nowotschin and Luke T. G. Harland and Ying-Yi Kuo and Bart Theeuwes and Berthold Göttgens and Elizabeth Lacy and Anna‐Katerina Hadjantonakis and Kathryn V. Anderson},
  journal = {Developmental Cell},
  year = {2026},
  month = jul,
  doi = {10.1016/j.devcel.2026.06.004},
  url = {https://doi.org/10.1016/j.devcel.2026.06.004},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - AXIN1 and AXIN2 regulate the WNT-signaling landscape to promote distinct mesoderm programs
AU  - Rocío Hernández-Martínez
AU  - Sonja Nowotschin
AU  - Luke T. G. Harland
AU  - Ying-Yi Kuo
AU  - Bart Theeuwes
AU  - Berthold Göttgens
AU  - Elizabeth Lacy
AU  - Anna‐Katerina Hadjantonakis
AU  - Kathryn V. Anderson
PY  - 2026
DA  - 2026/07/01
JO  - Developmental Cell
DO  - 10.1016/j.devcel.2026.06.004
UR  - https://doi.org/10.1016/j.devcel.2026.06.004
AB  - How distinct lineage identities are specified from pluripotent epiblast cells during gastrulation is a longstanding open question. By investigating AXIN, a negative regulator of the WNT/β-catenin pathway, we have uncovered previously unrecognized roles for WNT signaling in the specification of distinct mesoderm identities. Using complementary approaches, including a detailed analysis of Axin1;Axin2 mutant mouse embryos involving single-cell and single-embryo transcriptomics and in vitro pluripotent stem cell differentiation assays, our data revealed two critical layers of regulation. First, WNT initiates differentiation of primitive streak cells into mesoderm progenitors. Next, WNT amplifies and cooperates with bone morphogenetic protein (BMP)/pSMAD1/5/9 or NODAL/pSMAD2/3 to propel differentiating mesoderm progenitors into either posterior or anterior streak identities, respectively. We propose that Axin1 and Axin2 function to prevent precocious differentiation of pluripotent epiblast cells into mesoderm through the spatiotemporal regulation of WNT-signaling levels.
SN  - 1534-5807
SN  - 1878-1551
ER  -