Cargando…

Control of neural crest multipotency by Wnt signaling and the Lin28/let-7 axis

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 e...

Descripción completa

Detalles Bibliográficos
Autores principales: Bhattacharya, Debadrita, Rothstein, Megan, Azambuja, Ana Paula, Simoes-Costa, Marcos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6301792/
https://www.ncbi.nlm.nih.gov/pubmed/30520734
http://dx.doi.org/10.7554/eLife.40556
Descripción
Sumario: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.