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 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 signalling to 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 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.
A wave of WNT signalling balanced by secreted inhibitors controls primitive streak formation in micropattern colonies of human embryonic stem cells
Currently Viewing Accepted Manuscript - Newer Version Available
- Split-screen
- Views Icon Views
- PDF LinkPDF File PDFPDF+SI
-
Article Versions Icon
Versions
- Version of Record 25 March 2019
- Accepted Manuscript 01 January 2019
- Share Icon Share
-
Tools Icon
Tools
- Search Site
I. Martyn, A. H. Brivanlou, E. D. Siggia; A wave of WNT signalling balanced by secreted inhibitors controls primitive streak formation in micropattern colonies of human embryonic stem cells. Development 2019; dev.172791. doi: https://doi.org/10.1242/dev.172791
Download citation file:
Advertisement
Development Journal Meeting 2022: From Stem Cells to Human Development
-JournalMeeting.png?versionId=3737)
Following a virtual meeting in 2020, we are delighted to announce that the fifth iteration of our popular Journal Meeting will be held from 11-14 September 2022 at the historic Wotton House, Surrey. Registration is open now.
Special Issue: The Immune System in Development and Regeneration
(update)-ImmuneSI.png?versionId=3737)
Our latest special issue is now complete. It showcases articles that add to the repertoire of immune cell functions during development, repair and regeneration, and provide insights into the developmental pathways leading to the generation and dispersal of these cells.
Propose a new Workshop
-GSWorkshop.png?versionId=3737)
Our Workshops bring together leading experts and early-career researchers from a range of scientific backgrounds. Applications are now open to propose Workshops for 2024, one of which will be held in a Global South country.
Preprints in Development
(update)-InPreprints.png?versionId=3737)
As part of our efforts to support the use of preprints and help curate the preprint literature, we are delighted to launch a new article type: ‘In preprints’. These pieces will discuss one or more recent preprints and place them in a broader context. You can read the first article here.
FocalPlane Network launched
-FocalPlaneNetworkLaunch.png?versionId=3737)
Like the Node Network, the aim of the FocalPlane Network is to facilitate promotion and networking as well as assist those seeking conference speakers, committee members, reviewers or collaborators. We hope that it will help promote diversity in the community. Find out more and join the Network here.