Control of neural crest multipotency by Wnt signaling and the Lin28/let-7 axis
- Cornell University, United States
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.
Article and author information
Author details
Marcos Simoes-Costa
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.
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.
Metrics
-
- 3,472
- views
-
- 476
- downloads
-
- 49
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Control of neural crest multipotency by Wnt signaling and the Lin28/let-7 axis
eLife 7:e40556.
https://doi.org/10.7554/eLife.40556
