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An endodermal subpopulation generates neural and mesodermal fates in the posterior chick embryo

Preprint Created on 22 May 2026 bioRxiv

The discovery of neuromesodermal progenitors - a bipotent progenitor population in the tailbud that gives rise to traditionally ectodermal and mesodermal tissues - has disrupted the classical view that progenitors of the three distinct germ layers are exclusively segregated during gastrulation. However, until now the notion of lineage restriction of the endoderm to 'traditional' gastrointestinal tissues has largely remained intact. Here, we describe our discovery of a unique subpopulation in the chick endoderm that initially lines the ventral surface of the posterior organizer (Hensen's node), but at the trunk-to-tail developmental switch, undergoes an FGF-dependent epithelial-to-mesenchymal transition, giving rise to a remarkably broad range of cell types including somites, notochord, and neural tube. Strikingly, ablation of this endodermal cell population results in a severe ~50% reduction in axis elongation rate. Through single cell RNA sequencing and in situ hybridization chain reaction, we conclude that these cells lose their endodermal identity upon ingression, giving rise to effective NMPs. Lineage tracing reveals that the node endoderm harbors multipotent progenitors with clonal derivatives spanning endoderm and mesoderm or ectoderm. These findings illustrate a previously unappreciated endodermal source of NMPs, and further demonstrates the breakdown of traditional lineage restriction of germ layers in the posterior embryo.

Oikonomou, P., Calvary, L., Du, D., Polanksy, J., Gattoni, G., Lynch, C., Shi, L., Mayer, C., McFaline-Figueroa, J., Nerurkar, N. L.

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