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...
Autores principales: | , , , |
---|---|
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 |
_version_ | 1783381863679655936 |
---|---|
author | Bhattacharya, Debadrita Rothstein, Megan Azambuja, Ana Paula Simoes-Costa, Marcos |
author_facet | Bhattacharya, Debadrita Rothstein, Megan Azambuja, Ana Paula Simoes-Costa, Marcos |
author_sort | Bhattacharya, Debadrita |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6301792 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-63017922019-01-04 Control of neural crest multipotency by Wnt signaling and the Lin28/let-7 axis Bhattacharya, Debadrita Rothstein, Megan Azambuja, Ana Paula Simoes-Costa, Marcos eLife Developmental Biology 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. eLife Sciences Publications, Ltd 2018-12-06 /pmc/articles/PMC6301792/ /pubmed/30520734 http://dx.doi.org/10.7554/eLife.40556 Text en © 2018, Bhattacharya et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Developmental Biology Bhattacharya, Debadrita Rothstein, Megan Azambuja, Ana Paula Simoes-Costa, Marcos Control of neural crest multipotency by Wnt signaling and the Lin28/let-7 axis |
title | Control of neural crest multipotency by Wnt signaling and the Lin28/let-7 axis |
title_full | Control of neural crest multipotency by Wnt signaling and the Lin28/let-7 axis |
title_fullStr | Control of neural crest multipotency by Wnt signaling and the Lin28/let-7 axis |
title_full_unstemmed | Control of neural crest multipotency by Wnt signaling and the Lin28/let-7 axis |
title_short | Control of neural crest multipotency by Wnt signaling and the Lin28/let-7 axis |
title_sort | control of neural crest multipotency by wnt signaling and the lin28/let-7 axis |
topic | Developmental Biology |
url | 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 |
work_keys_str_mv | AT bhattacharyadebadrita controlofneuralcrestmultipotencybywntsignalingandthelin28let7axis AT rothsteinmegan controlofneuralcrestmultipotencybywntsignalingandthelin28let7axis AT azambujaanapaula controlofneuralcrestmultipotencybywntsignalingandthelin28let7axis AT simoescostamarcos controlofneuralcrestmultipotencybywntsignalingandthelin28let7axis |