Intercellular exchange of Wnt ligands reduces cell population heterogeneity during embryogenesis

Yudai Hatakeyama, Nen Saito (), Yusuke Mii, Ritsuko Takada, Takuma Shinozuka, Tatsuya Takemoto, Honda Naoki and Shinji Takada ()
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Yudai Hatakeyama: National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji-cho
Nen Saito: National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji-cho
Yusuke Mii: National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji-cho
Ritsuko Takada: National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji-cho
Takuma Shinozuka: National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji-cho
Tatsuya Takemoto: Tokushima University, 3-18-5 Kuramoto-cho
Honda Naoki: National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji-cho
Shinji Takada: National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji-cho

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-37350-x

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