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

Autor:	Hernández-Martínez R; Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Nowotschin S; Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Harland LTG; Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Haematology, University of Cambridge, Cambridge, UK., Kuo YY; Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Theeuwes B; Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Haematology, University of Cambridge, Cambridge, UK., Göttgens B; Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Haematology, University of Cambridge, Cambridge, UK., Lacy E; Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Hadjantonakis AK; Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Anderson KV; Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Sep 11. Date of Electronic Publication: 2024 Sep 11.
DOI:	10.1101/2024.09.11.612342
Abstrakt:	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 Axin1 ; Axin2 mutant mouse embryos, including single-cell and single-embryo transcriptomics, with in vitro 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 Axin1 and Axin2 prevent aberrant differentiation of pluripotent epiblast cells into mesoderm by spatially and temporally regulating WNT signaling levels. Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.
Databáze:	MEDLINE
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