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Differential compartmentalization of BMP4/NOGGIN requires NOGGIN trans-epithelial transport

Cornell Affiliated Author(s)

Author

T. Phan-Everson
F. Etoc
S. Li
S. Khodursky
A. Yoney
A.H. Brivanlou
E.D. Siggia

Abstract

Using self-organizing human models of gastrulation, we previously showed that (1) BMP4 initiates the cascade of events leading to gastrulation, (2) BMP4 signal reception is restricted to the basolateral domain, and (3) in a human-specific manner, BMP4 directly induces the expression of NOGGIN. Here, we report the surprising discovery that in human epiblasts, NOGGIN and BMP4 were secreted into opposite extracellular spaces. Interestingly, apically presented NOGGIN could inhibit basally delivered BMP4. Apically imposed microfluidic flow demonstrated that NOGGIN traveled in the apical extracellular space. Our co-localization analysis detailed the endocytotic route that trafficked NOGGIN from the apical space to the basolateral intercellular space where BMP4 receptors were located. This apical-basal transcytosis was indispensable for NOGGIN inhibition. Taken together, the segregation of activator/inhibitor into distinct extracellular spaces challenges classical views of morphogen movement. We propose that the transport of morphogen inhibitors regulates the spatial availability of morphogens during embryogenesis. © 2021 Elsevier Inc.

Date Published

Journal

Developmental Cell

Volume

56

Issue

13

Number of Pages

1930-1944.e5,

URL

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85109461157&doi=10.1016%2fj.devcel.2021.05.003&partnerID=40&md5=475bd22764d6833951357fb38d07125c

DOI

10.1016/j.devcel.2021.05.003

Research Area

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