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Self-organization of a human organizer by combined Wnt and Nodal signaling

Cornell Affiliated Author(s)

Author

I. Martyn
T.Y. Kanno
A. Ruzo
E.D. Siggia
A.H. Brivanlou

Abstract

In amniotes, the development of the primitive streak and its accompanying 'organizer' define the first stages of gastrulation. Although these structures have been characterized in detail in model organisms, the human primitive streak and organizer remain a mystery. When stimulated with BMP4, micropatterned colonies of human embryonic stem cells self-organize to generate early embryonic germ layers 1 . Here we show that, in the same type of colonies, Wnt signalling is sufficient to induce a primitive streak, and stimulation with Wnt and Activin is sufficient to induce an organizer, as characterized by embryo-like sharp boundary formation, markers of epithelial-to-mesenchymal transition and expression of the organizer-specific transcription factor GSC. Moreover, when grafted into chick embryos, human stem cell colonies treated with Wnt and Activin induce and contribute autonomously to a secondary axis while inducing a neural fate in the host. This fulfils the most stringent functional criteria for an organizer, and its discovery represents a milestone in human embryology. © 2018 Macmillan Publishers Ltd., part of Springer Nature.

Date Published

Journal

Nature

Volume

558

Issue

7708

Number of Pages

132-135,

URL

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85048242238&doi=10.1038%2fs41586-018-0150-y&partnerID=40&md5=4077c22e3d5bf4f8edf2bb6036182f59

DOI

10.1038/s41586-018-0150-y

Research Area

Funding Source

2016-007
R01HD080699

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