Intercellular exchange of Wnt ligands reduces cell population heterogeneity during embryogenesis

• Published in: Nature communications 2023-04, Vol.14 (1), p.1924-1924, Article 1924
• Main Authors: Hatakeyama, Yudai, Saito, Nen, Mii, Yusuke, Takada, Ritsuko, Shinozuka, Takuma, Takemoto, Tatsuya, Naoki, Honda, Takada, Shinji
• Format: Article
• Language: English
• Subjects: 13; 38; 38/1; 38/71; 42/109; 42/41; 45/23; 45/77; 631/136/1660/2127; 631/136/2086/1456; 631/80/86/2370; 96; Animals; Cell Differentiation - genetics; Embryogenesis; Embryonic Development - genetics; Embryonic growth stage; Embryos; Environmental stress; Exchanging; Gene Expression Regulation, Developmental; Germ Layers; Heterogeneity; Humanities and Social Sciences; Ligands; Maintenance; Mesoderm; Mice; multidisciplinary; Neural stem cells; Phenotypes; Retinoic acid; Science; Science (multidisciplinary); Signaling; Wnt protein; Wnt Signaling Pathway - physiology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-37350-x

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. Neuromesodermal progenitor (NMP) cells produce and receive Wnt ligands. Here, the authors show that mutual intercellular exchange of Wnt ligands reduces heterogeneity between NMP cells and makes NMP populations robust to environmental stress.