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

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

Posted 10 Oct 2018
bioRxiv DOI: 10.1101/440602 (published DOI: 10.1242/dev.172791)

Long range signalling 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 gastruloid 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 signalling to colony border. Following application of WNT ligand, E-CAD mediates a 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 CERBERUS1 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 a single quantitative model describes both the wave and our knockout data.

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