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PRDM16 regulates a temporal transcriptional program to promote progression of cortical neural progenitors

Radial glia (RG) in the neocortex sequentially generate distinct subtypes of projection neurons, accounting for the diversity and complex assembly of cortical neural circuits. Mechanisms that drive the rapid and precise temporal progression of RG are beginning to be elucidated. Here, we reveal that...

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Autores principales: He, Li, Jones, Jennifer, He, Weiguo, Bjork, Bryan C., Wen, Jiayu, Dai, Qi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990860/
https://www.ncbi.nlm.nih.gov/pubmed/33597191
http://dx.doi.org/10.1242/dev.194670
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author He, Li
Jones, Jennifer
He, Weiguo
Bjork, Bryan C.
Wen, Jiayu
Dai, Qi
author_facet He, Li
Jones, Jennifer
He, Weiguo
Bjork, Bryan C.
Wen, Jiayu
Dai, Qi
author_sort He, Li
collection PubMed
description Radial glia (RG) in the neocortex sequentially generate distinct subtypes of projection neurons, accounting for the diversity and complex assembly of cortical neural circuits. Mechanisms that drive the rapid and precise temporal progression of RG are beginning to be elucidated. Here, we reveal that the RG-specific transcriptional regulator PRDM16 promotes the transition of early to late phase of neurogenesis in the mouse neocortex. Loss of Prdm16 delays the timely progression of RG, leading to defective cortical laminar organization. Our genomic analyses demonstrate that PRDM16 regulates a subset of genes that are dynamically expressed between early and late neurogenesis. We show that PRDM16 suppresses target gene expression through limiting chromatin accessibility of permissive enhancers. We further confirm that crucial target genes regulated by PRDM16 are neuronal specification genes, cell cycle regulators and molecules required for neuronal migration. These findings provide evidence to support the finding that neural progenitors temporally shift the gene expression program to achieve neural cell diversity.
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spelling pubmed-79908602021-03-30 PRDM16 regulates a temporal transcriptional program to promote progression of cortical neural progenitors He, Li Jones, Jennifer He, Weiguo Bjork, Bryan C. Wen, Jiayu Dai, Qi Development Stem Cells and Regeneration Radial glia (RG) in the neocortex sequentially generate distinct subtypes of projection neurons, accounting for the diversity and complex assembly of cortical neural circuits. Mechanisms that drive the rapid and precise temporal progression of RG are beginning to be elucidated. Here, we reveal that the RG-specific transcriptional regulator PRDM16 promotes the transition of early to late phase of neurogenesis in the mouse neocortex. Loss of Prdm16 delays the timely progression of RG, leading to defective cortical laminar organization. Our genomic analyses demonstrate that PRDM16 regulates a subset of genes that are dynamically expressed between early and late neurogenesis. We show that PRDM16 suppresses target gene expression through limiting chromatin accessibility of permissive enhancers. We further confirm that crucial target genes regulated by PRDM16 are neuronal specification genes, cell cycle regulators and molecules required for neuronal migration. These findings provide evidence to support the finding that neural progenitors temporally shift the gene expression program to achieve neural cell diversity. The Company of Biologists Ltd 2021-03-17 /pmc/articles/PMC7990860/ /pubmed/33597191 http://dx.doi.org/10.1242/dev.194670 Text en © 2021. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/4.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Stem Cells and Regeneration
He, Li
Jones, Jennifer
He, Weiguo
Bjork, Bryan C.
Wen, Jiayu
Dai, Qi
PRDM16 regulates a temporal transcriptional program to promote progression of cortical neural progenitors
title PRDM16 regulates a temporal transcriptional program to promote progression of cortical neural progenitors
title_full PRDM16 regulates a temporal transcriptional program to promote progression of cortical neural progenitors
title_fullStr PRDM16 regulates a temporal transcriptional program to promote progression of cortical neural progenitors
title_full_unstemmed PRDM16 regulates a temporal transcriptional program to promote progression of cortical neural progenitors
title_short PRDM16 regulates a temporal transcriptional program to promote progression of cortical neural progenitors
title_sort prdm16 regulates a temporal transcriptional program to promote progression of cortical neural progenitors
topic Stem Cells and Regeneration
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990860/
https://www.ncbi.nlm.nih.gov/pubmed/33597191
http://dx.doi.org/10.1242/dev.194670
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