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Cell-Type-Specific Gene Expression in Developing Mouse Neocortex: Intermediate Progenitors Implicated in Axon Development

Cerebral cortex projection neurons (PNs) are generated from intermediate progenitors (IPs), which are in turn derived from radial glial progenitors (RGPs). To investigate developmental processes in IPs, we profiled IP transcriptomes in embryonic mouse neocortex, using transgenic Tbr2-GFP mice, cell...

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Autores principales: Bedogni, Francesco, Hevner, Robert F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313239/
https://www.ncbi.nlm.nih.gov/pubmed/34321999
http://dx.doi.org/10.3389/fnmol.2021.686034
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author Bedogni, Francesco
Hevner, Robert F.
author_facet Bedogni, Francesco
Hevner, Robert F.
author_sort Bedogni, Francesco
collection PubMed
description Cerebral cortex projection neurons (PNs) are generated from intermediate progenitors (IPs), which are in turn derived from radial glial progenitors (RGPs). To investigate developmental processes in IPs, we profiled IP transcriptomes in embryonic mouse neocortex, using transgenic Tbr2-GFP mice, cell sorting, and microarrays. These data were used in combination with in situ hybridization to ascertain gene sets specific for IPs, RGPs, PNs, interneurons, and other neural and non-neural cell types. RGP-selective transcripts (n = 419) included molecules for Notch receptor signaling, proliferation, neural stem cell identity, apical junctions, necroptosis, hippo pathway, and NF-κB pathway. RGPs also expressed specific genes for critical interactions with meningeal and vascular cells. In contrast, IP-selective genes (n = 136) encoded molecules for activated Delta ligand presentation, epithelial-mesenchymal transition, core planar cell polarity (PCP), axon genesis, and intrinsic excitability. Interestingly, IPs expressed several “dependence receptors” (Unc5d, Dcc, Ntrk3, and Epha4) that induce apoptosis in the absence of ligand, suggesting a competitive mechanism for IPs and new PNs to detect key environmental cues or die. Overall, our results imply a novel role for IPs in the patterning of neuronal polarization, axon differentiation, and intrinsic excitability prior to mitosis. Significantly, IPs highly express Wnt-PCP, netrin, and semaphorin pathway molecules known to regulate axon polarization in other systems. In sum, IPs not only amplify neurogenesis quantitatively, but also molecularly “prime” new PNs for axogenesis, guidance, and excitability.
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spelling pubmed-83132392021-07-27 Cell-Type-Specific Gene Expression in Developing Mouse Neocortex: Intermediate Progenitors Implicated in Axon Development Bedogni, Francesco Hevner, Robert F. Front Mol Neurosci Neuroscience Cerebral cortex projection neurons (PNs) are generated from intermediate progenitors (IPs), which are in turn derived from radial glial progenitors (RGPs). To investigate developmental processes in IPs, we profiled IP transcriptomes in embryonic mouse neocortex, using transgenic Tbr2-GFP mice, cell sorting, and microarrays. These data were used in combination with in situ hybridization to ascertain gene sets specific for IPs, RGPs, PNs, interneurons, and other neural and non-neural cell types. RGP-selective transcripts (n = 419) included molecules for Notch receptor signaling, proliferation, neural stem cell identity, apical junctions, necroptosis, hippo pathway, and NF-κB pathway. RGPs also expressed specific genes for critical interactions with meningeal and vascular cells. In contrast, IP-selective genes (n = 136) encoded molecules for activated Delta ligand presentation, epithelial-mesenchymal transition, core planar cell polarity (PCP), axon genesis, and intrinsic excitability. Interestingly, IPs expressed several “dependence receptors” (Unc5d, Dcc, Ntrk3, and Epha4) that induce apoptosis in the absence of ligand, suggesting a competitive mechanism for IPs and new PNs to detect key environmental cues or die. Overall, our results imply a novel role for IPs in the patterning of neuronal polarization, axon differentiation, and intrinsic excitability prior to mitosis. Significantly, IPs highly express Wnt-PCP, netrin, and semaphorin pathway molecules known to regulate axon polarization in other systems. In sum, IPs not only amplify neurogenesis quantitatively, but also molecularly “prime” new PNs for axogenesis, guidance, and excitability. Frontiers Media S.A. 2021-07-12 /pmc/articles/PMC8313239/ /pubmed/34321999 http://dx.doi.org/10.3389/fnmol.2021.686034 Text en Copyright © 2021 Bedogni and Hevner. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Bedogni, Francesco
Hevner, Robert F.
Cell-Type-Specific Gene Expression in Developing Mouse Neocortex: Intermediate Progenitors Implicated in Axon Development
title Cell-Type-Specific Gene Expression in Developing Mouse Neocortex: Intermediate Progenitors Implicated in Axon Development
title_full Cell-Type-Specific Gene Expression in Developing Mouse Neocortex: Intermediate Progenitors Implicated in Axon Development
title_fullStr Cell-Type-Specific Gene Expression in Developing Mouse Neocortex: Intermediate Progenitors Implicated in Axon Development
title_full_unstemmed Cell-Type-Specific Gene Expression in Developing Mouse Neocortex: Intermediate Progenitors Implicated in Axon Development
title_short Cell-Type-Specific Gene Expression in Developing Mouse Neocortex: Intermediate Progenitors Implicated in Axon Development
title_sort cell-type-specific gene expression in developing mouse neocortex: intermediate progenitors implicated in axon development
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313239/
https://www.ncbi.nlm.nih.gov/pubmed/34321999
http://dx.doi.org/10.3389/fnmol.2021.686034
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