Control of neural crest multipotency by Wnt signaling and the Lin28/let-7 axis
Abstract
A crucial step in cell differentiation is the silencing of developmental programs underlying multipotency. While much is known about how lineage-specific genes are activated to generate distinct cell types, the mechanisms driving suppression of stemness are far less understood. To address this, we examined the regulation of the transcriptional network that maintains progenitor identity in avian neural crest cells. Our results show that a regulatory circuit formed by Wnt, Lin28a and let-7 miRNAs controls the deployment and the subsequent silencing of the multipotency program in a position-dependent manner. Transition from multipotency to differentiation is determined by the topological relationship between the migratory cells and the dorsal neural tube, which acts as a Wnt-producing stem cell niche. Our findings highlight a mechanism that rapidly silences complex regulatory programs, and elucidate how transcriptional networks respond to positional information during cell differentiation.
Data availability
All data generated for this study are included in the manuscript and supporting files. Source data files have been provided for all figures.
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Author details
Funding
National Institute of Dental and Craniofacial Research
- Marcos Simoes-Costa
March of Dimes Foundation
- Marcos Simoes-Costa
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Richard M White, Memorial Sloan Kettering Cancer Center, United States
Publication history
- Received: July 28, 2018
- Accepted: December 4, 2018
- Accepted Manuscript published: December 6, 2018 (version 1)
- Version of Record published: December 20, 2018 (version 2)
Copyright
© 2018, Bhattacharya et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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