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A wave of WNT signaling balanced by secreted inhibitors controls primitive streak formation in micropattern colonies of human embryonic stem cells

Cornell Affiliated Author(s)

Author

I. Martyn
A.H. Brivanlou
E.D. Siggia

Abstract

Long-range signaling by morphogens and their inhibitors define embryonic patterning yet quantitative data and models are rare, especially in humans. Here, we use a human embryonic stem cell micropattern system to model formation of the primitive streak (PS) by WNT. In the pluripotent state, E-cadherin (E-CAD) transduces boundary forces to focus WNT signaling to the colony border. Following application of WNT ligand, E-CAD mediates a front or wave of epithelial-to-mesenchymal (EMT) conversion analogous to PS extension in an embryo. By knocking out the secreted WNT inhibitors active in our system, we show that DKK1 alone controls the extent and duration of patterning. The NODAL inhibitor cerberus 1 acts downstream of WNT to refine the endoderm versus mesoderm fate choice. Our EMT wave is a generic property of a bistable system with diffusion and we present a single quantitative model that describes both the wave and our knockout data. © 2019. Published by The Company of Biologists Ltd.

Date Published

Journal

Development (Cambridge)

Volume

146

Issue

6

URL

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85063711684&doi=10.1242%2fdev.172791&partnerID=40&md5=3355e2295bc658dd70fb0474057d921c

DOI

10.1242/dev.172791

Research Area

Funding Source

PHY 1502151
R01 HD080699
R01GM101653

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