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...

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书目详细资料
Main Authors: Debadrita Bhattacharya, Megan Rothstein, Ana Paula Azambuja, Marcos Simoes-Costa
格式: 文件
语言:English
出版: eLife Sciences Publications Ltd 2018-12-01
丛编:eLife
主题:
在线阅读:https://elifesciences.org/articles/40556
实物特征
总结: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.
ISSN:2050-084X