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An atlas of cortical arealization identifies dynamic molecular signatures

The human brain is subdivided into distinct anatomical structures, including the neocortex, which in turn encompasses dozens of distinct specialized cortical areas. Early morphogenetic gradients are known to establish early brain regions and cortical areas, but how early patterns result in finer and...

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Autores principales: Bhaduri, Aparna, Sandoval-Espinosa, Carmen, Otero-Garcia, Marcos, Oh, Irene, Yin, Raymund, Eze, Ugomma C., Nowakowski, Tomasz J., Kriegstein, Arnold R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494648/
https://www.ncbi.nlm.nih.gov/pubmed/34616070
http://dx.doi.org/10.1038/s41586-021-03910-8
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author Bhaduri, Aparna
Sandoval-Espinosa, Carmen
Otero-Garcia, Marcos
Oh, Irene
Yin, Raymund
Eze, Ugomma C.
Nowakowski, Tomasz J.
Kriegstein, Arnold R.
author_facet Bhaduri, Aparna
Sandoval-Espinosa, Carmen
Otero-Garcia, Marcos
Oh, Irene
Yin, Raymund
Eze, Ugomma C.
Nowakowski, Tomasz J.
Kriegstein, Arnold R.
author_sort Bhaduri, Aparna
collection PubMed
description The human brain is subdivided into distinct anatomical structures, including the neocortex, which in turn encompasses dozens of distinct specialized cortical areas. Early morphogenetic gradients are known to establish early brain regions and cortical areas, but how early patterns result in finer and more discrete spatial differences remains poorly understood(1). Here we use single-cell RNA sequencing to profile ten major brain structures and six neocortical areas during peak neurogenesis and early gliogenesis. Within the neocortex, we find that early in the second trimester, a large number of genes are differentially expressed across distinct cortical areas in all cell types, including radial glia, the neural progenitors of the cortex. However, the abundance of areal transcriptomic signatures increases as radial glia differentiate into intermediate progenitor cells and ultimately give rise to excitatory neurons. Using an automated, multiplexed single-molecule fluorescent in situ hybridization approach, we find that laminar gene-expression patterns are highly dynamic across cortical regions. Together, our data suggest that early cortical areal patterning is defined by strong, mutually exclusive frontal and occipital gene-expression signatures, with resulting gradients giving rise to the specification of areas between these two poles throughout successive developmental timepoints.
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spelling pubmed-84946482021-10-19 An atlas of cortical arealization identifies dynamic molecular signatures Bhaduri, Aparna Sandoval-Espinosa, Carmen Otero-Garcia, Marcos Oh, Irene Yin, Raymund Eze, Ugomma C. Nowakowski, Tomasz J. Kriegstein, Arnold R. Nature Article The human brain is subdivided into distinct anatomical structures, including the neocortex, which in turn encompasses dozens of distinct specialized cortical areas. Early morphogenetic gradients are known to establish early brain regions and cortical areas, but how early patterns result in finer and more discrete spatial differences remains poorly understood(1). Here we use single-cell RNA sequencing to profile ten major brain structures and six neocortical areas during peak neurogenesis and early gliogenesis. Within the neocortex, we find that early in the second trimester, a large number of genes are differentially expressed across distinct cortical areas in all cell types, including radial glia, the neural progenitors of the cortex. However, the abundance of areal transcriptomic signatures increases as radial glia differentiate into intermediate progenitor cells and ultimately give rise to excitatory neurons. Using an automated, multiplexed single-molecule fluorescent in situ hybridization approach, we find that laminar gene-expression patterns are highly dynamic across cortical regions. Together, our data suggest that early cortical areal patterning is defined by strong, mutually exclusive frontal and occipital gene-expression signatures, with resulting gradients giving rise to the specification of areas between these two poles throughout successive developmental timepoints. Nature Publishing Group UK 2021-10-06 2021 /pmc/articles/PMC8494648/ /pubmed/34616070 http://dx.doi.org/10.1038/s41586-021-03910-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Bhaduri, Aparna
Sandoval-Espinosa, Carmen
Otero-Garcia, Marcos
Oh, Irene
Yin, Raymund
Eze, Ugomma C.
Nowakowski, Tomasz J.
Kriegstein, Arnold R.
An atlas of cortical arealization identifies dynamic molecular signatures
title An atlas of cortical arealization identifies dynamic molecular signatures
title_full An atlas of cortical arealization identifies dynamic molecular signatures
title_fullStr An atlas of cortical arealization identifies dynamic molecular signatures
title_full_unstemmed An atlas of cortical arealization identifies dynamic molecular signatures
title_short An atlas of cortical arealization identifies dynamic molecular signatures
title_sort atlas of cortical arealization identifies dynamic molecular signatures
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494648/
https://www.ncbi.nlm.nih.gov/pubmed/34616070
http://dx.doi.org/10.1038/s41586-021-03910-8
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