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FOXP1 orchestrates neurogenesis in human cortical basal radial glial cells

During cortical development, human basal radial glial cells (bRGCs) are highly capable of sustained self-renewal and neurogenesis. Selective pressures on this cell type may have contributed to the evolution of the human neocortex, leading to an increase in cortical size. bRGCs have enriched expressi...

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Autores principales: Park, Seon Hye E., Kulkarni, Ashwinikumar, Konopka, Genevieve
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10431666/
https://www.ncbi.nlm.nih.gov/pubmed/37540706
http://dx.doi.org/10.1371/journal.pbio.3001852
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author Park, Seon Hye E.
Kulkarni, Ashwinikumar
Konopka, Genevieve
author_facet Park, Seon Hye E.
Kulkarni, Ashwinikumar
Konopka, Genevieve
author_sort Park, Seon Hye E.
collection PubMed
description During cortical development, human basal radial glial cells (bRGCs) are highly capable of sustained self-renewal and neurogenesis. Selective pressures on this cell type may have contributed to the evolution of the human neocortex, leading to an increase in cortical size. bRGCs have enriched expression for Forkhead Box P1 (FOXP1), a transcription factor implicated in neurodevelopmental disorders (NDDs) such as autism spectrum disorder. However, the cell type–specific roles of FOXP1 in bRGCs during cortical development remain unexplored. Here, we examine the requirement for FOXP1 gene expression regulation underlying the production of bRGCs using human brain organoids. We examine a developmental time point when FOXP1 expression is highest in the cortical progenitors, and the bRGCs, in particular, begin to actively produce neurons. With the loss of FOXP1, we show a reduction in the number of bRGCs, as well as reduced proliferation and differentiation of the remaining bRGCs, all of which lead to reduced numbers of excitatory cortical neurons over time. Using single-nuclei RNA sequencing and cell trajectory analysis, we uncover a role for FOXP1 in directing cortical progenitor proliferation and differentiation by regulating key signaling pathways related to neurogenesis and NDDs. Together, these results demonstrate that FOXP1 regulates human-specific features in early cortical development.
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spelling pubmed-104316662023-08-17 FOXP1 orchestrates neurogenesis in human cortical basal radial glial cells Park, Seon Hye E. Kulkarni, Ashwinikumar Konopka, Genevieve PLoS Biol Short Reports During cortical development, human basal radial glial cells (bRGCs) are highly capable of sustained self-renewal and neurogenesis. Selective pressures on this cell type may have contributed to the evolution of the human neocortex, leading to an increase in cortical size. bRGCs have enriched expression for Forkhead Box P1 (FOXP1), a transcription factor implicated in neurodevelopmental disorders (NDDs) such as autism spectrum disorder. However, the cell type–specific roles of FOXP1 in bRGCs during cortical development remain unexplored. Here, we examine the requirement for FOXP1 gene expression regulation underlying the production of bRGCs using human brain organoids. We examine a developmental time point when FOXP1 expression is highest in the cortical progenitors, and the bRGCs, in particular, begin to actively produce neurons. With the loss of FOXP1, we show a reduction in the number of bRGCs, as well as reduced proliferation and differentiation of the remaining bRGCs, all of which lead to reduced numbers of excitatory cortical neurons over time. Using single-nuclei RNA sequencing and cell trajectory analysis, we uncover a role for FOXP1 in directing cortical progenitor proliferation and differentiation by regulating key signaling pathways related to neurogenesis and NDDs. Together, these results demonstrate that FOXP1 regulates human-specific features in early cortical development. Public Library of Science 2023-08-04 /pmc/articles/PMC10431666/ /pubmed/37540706 http://dx.doi.org/10.1371/journal.pbio.3001852 Text en © 2023 Park et al https://creativecommons.org/licenses/by/4.0/This 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 the original author and source are credited.
spellingShingle Short Reports
Park, Seon Hye E.
Kulkarni, Ashwinikumar
Konopka, Genevieve
FOXP1 orchestrates neurogenesis in human cortical basal radial glial cells
title FOXP1 orchestrates neurogenesis in human cortical basal radial glial cells
title_full FOXP1 orchestrates neurogenesis in human cortical basal radial glial cells
title_fullStr FOXP1 orchestrates neurogenesis in human cortical basal radial glial cells
title_full_unstemmed FOXP1 orchestrates neurogenesis in human cortical basal radial glial cells
title_short FOXP1 orchestrates neurogenesis in human cortical basal radial glial cells
title_sort foxp1 orchestrates neurogenesis in human cortical basal radial glial cells
topic Short Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10431666/
https://www.ncbi.nlm.nih.gov/pubmed/37540706
http://dx.doi.org/10.1371/journal.pbio.3001852
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