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A balance between secreted inhibitors and edge sensing controls gastruloid self-organization

Item Type:Article
Title:A balance between secreted inhibitors and edge sensing controls gastruloid self-organization
Creators Name:Etoc, F. and Metzger, J. and Ruzo, A. and Kirst, C. and Yoney, A. and Ozair, M.Z. and Brivanlou, A.H. and Siggia, E.D.
Abstract:The earliest aspects of human embryogenesis remain mysterious. To model patterning events in the human embryo, we used colonies of human embryonic stem cells (hESCs) grown on micropatterned substrate and differentiated with BMP4. These gastruloids recapitulate the embryonic arrangement of the mammalian germ layers and provide an assay to assess the structural and signaling mechanisms patterning the human gastrula. Structurally, high-density hESCs localize their receptors to transforming growth factor β at their lateral side in the center of the colony while maintaining apical localization of receptors at the edge. This relocalization insulates cells at the center from apically applied ligands while maintaining response to basally presented ones. In addition, BMP4 directly induces the expression of its own inhibitor, NOGGIN, generating a reaction-diffusion mechanism that underlies patterning. We develop a quantitative model that integrates edge sensing and inhibitors to predict human fate positioning in gastruloids and, potentially, the human embryo.
Keywords:Self-Organization, Human Gastrulation, Gastruloid, Human Embryonic Stem Cell, Embryonic Patterning, Reaction-Diffusion, Bone Morphogenetic Protein, NOGGIN, Polarized Epithelium, Animals, Mice
Source:Developmental Cell
Publisher:Cell Press
Page Range:302-315
Date:7 November 2016
Official Publication:https://doi.org/10.1016/j.devcel.2016.09.016
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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