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Updated: Feb 1, 2026
Modeling Paracrine Noncanonical Wnt Signaling In Vitro
Published on: December 10, 2021
Control of neural crest multipotency by Wnt signaling and the Lin28/let-7 axis
Debadrita Bhattacharya1, Megan Rothstein1, Ana Paula Azambuja1
1Department of Molecular Biology and Genetics, Cornell University, Ithaca, 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.
Insights
Stemness is silenced during cell differentiation by a Wnt, Lin28a, and let-7 miRNA circuit. Positional information from the stem cell niche controls this process in avian neural crest cells.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Molecular Biology
Background:
- Cell differentiation involves silencing stemness programs, but mechanisms are poorly understood.
- Activating lineage-specific genes is known, but suppressing multipotency requires further investigation.
Purpose of the Study:
- To investigate the regulation of the transcriptional network maintaining progenitor identity in avian neural crest cells.
- To understand how stemness is suppressed during cell differentiation.
Main Methods:
- Examined the regulatory circuit involving Wnt, Lin28a, and let-7 miRNAs.
- Analyzed the role of positional information from the dorsal neural tube stem cell niche.
Main Results:
- A regulatory circuit of Wnt, Lin28a, and let-7 miRNAs controls multipotency program deployment and silencing.
- The transition from multipotency to differentiation depends on cell position relative to the Wnt-producing dorsal neural tube niche.
- Positional information dictates the silencing of complex regulatory programs.
Conclusions:
- A novel mechanism for rapid silencing of complex regulatory programs in cell differentiation.
- Elucidates how transcriptional networks integrate positional cues for differentiation.
- Provides insights into the suppression of stemness during development.
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