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Publication : Intercellular exchange of Wnt ligands reduces cell population heterogeneity during embryogenesis.

First Author  Hatakeyama Y Year  2023
Journal  Nat Commun Volume  14
Issue  1 Pages  1924
PubMed ID  37024462 Mgi Jnum  J:334609
Mgi Id  MGI:7460743 Doi  10.1038/s41467-023-37350-x
Citation  Hatakeyama Y, et al. (2023) Intercellular exchange of Wnt ligands reduces cell population heterogeneity during embryogenesis. Nat Commun 14(1):1924
abstractText  Wnt signaling is required to maintain bipotent progenitors for neural and paraxial mesoderm cells, the neuromesodermal progenitor (NMP) cells that reside in the epiblast and tailbud. Since epiblast/tailbud cells receive Wnt ligands produced by one another, this exchange may average out the heterogeneity of Wnt signaling levels among these cells. Here, we examined this possibility by replacing endogenous Wnt3a with a receptor-fused form that activates signaling in producing cells, but not in neighboring cells. Mutant mouse embryos show a unique phenotype in which maintenance of many NMP cells is impaired, although some cells persist for long periods. The epiblast cell population of these embryos increases heterogeneity in Wnt signaling levels as embryogenesis progresses and are sensitive to retinoic acid, an endogenous antagonist of NMP maintenance. Thus, mutual intercellular exchange of Wnt ligands in the epiblast cell population reduces heterogeneity and achieves robustness to environmental stress.
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