Dissecting signaling hierarchies in the patterning of the mouse primitive streak using micropatterned EpiLC colonies.

Jean-Louis Plouhinec, Gaël Simon, Mathieu Vieira, Jérôme Collignon, Benoit Sorre

Stem cell reports 2022 Jul 12

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Embryo studies have established that the patterning of the mouse gastrula depends on a regulatory network in which the WNT, BMP, and NODAL signaling pathways cooperate, but aspects of their respective contributions remain unclear. Studying their impact on the spatial organization and developmental trajectories of micropatterned epiblast-like cell (EpiLC) colonies, we show that NODAL is required prior to BMP action to establish the mesoderm and endoderm lineages. The presence of BMP then forces NODAL and WNT to support the formation of posterior primitive streak (PS) derivatives, while its absence allows them to promote that of anterior PS derivatives. Also, a Nodal mutation elicits more severe patterning defects in vitro than in the embryo, suggesting that ligands of extra-embryonic origin can rescue them. These results support the implication of a combinatorial process in PS patterning and illustrate how the study of micropatterned EpiLC colonies can complement that of embryos. Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Jean-Louis Plouhinec, Gaël Simon, Mathieu Vieira, Jérôme Collignon, Benoit Sorre. Dissecting signaling hierarchies in the patterning of the mouse primitive streak using micropatterned EpiLC colonies. Stem cell reports. 2022 Jul 12;17(7):1757-1771