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Meningeal retinoic acid contributes to neocortical lamination and radial migration during mouse brain development
Retinoic acid (RA) is a diffusible molecule involved in early forebrain patterning. Its later production in the meninges by the retinaldehyde dehydrogenase RALDH2 coincides with the time of cortical neuron generation. A function of RA in this process has not been adressed directly as Raldh2(−/−) mou...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312094/ https://www.ncbi.nlm.nih.gov/pubmed/28011626 http://dx.doi.org/10.1242/bio.021063 |
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author | Haushalter, Carole Schuhbaur, Brigitte Dollé, Pascal Rhinn, Muriel |
author_facet | Haushalter, Carole Schuhbaur, Brigitte Dollé, Pascal Rhinn, Muriel |
author_sort | Haushalter, Carole |
collection | PubMed |
description | Retinoic acid (RA) is a diffusible molecule involved in early forebrain patterning. Its later production in the meninges by the retinaldehyde dehydrogenase RALDH2 coincides with the time of cortical neuron generation. A function of RA in this process has not been adressed directly as Raldh2(−/−) mouse mutants are embryonic lethal. Here, we used a conditional genetic strategy to inactivate Raldh2 just prior to onset of its expression in the developing meninges. This inactivation does not affect the formation of the cortical progenitor populations, their rate of division, or timing of differentiation. However, migration of late-born cortical neurons is delayed, with neurons stalling in the intermediate zone and exhibiting an abnormal multipolar morphology. This suggests that RA controls the multipolar-to-bipolar transition that occurs in the intermediate zone and allows neurons to start locomotion in the cortical plate. Our work also shows a role for RA in cortical lamination, as deep layers are expanded and a subset of layer IV neurons are not formed in the Raldh2-ablated mutants. These data demonstrate that meninges are a source of extrinsic signals important for cortical development. |
format | Online Article Text |
id | pubmed-5312094 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-53120942017-03-06 Meningeal retinoic acid contributes to neocortical lamination and radial migration during mouse brain development Haushalter, Carole Schuhbaur, Brigitte Dollé, Pascal Rhinn, Muriel Biol Open Research Article Retinoic acid (RA) is a diffusible molecule involved in early forebrain patterning. Its later production in the meninges by the retinaldehyde dehydrogenase RALDH2 coincides with the time of cortical neuron generation. A function of RA in this process has not been adressed directly as Raldh2(−/−) mouse mutants are embryonic lethal. Here, we used a conditional genetic strategy to inactivate Raldh2 just prior to onset of its expression in the developing meninges. This inactivation does not affect the formation of the cortical progenitor populations, their rate of division, or timing of differentiation. However, migration of late-born cortical neurons is delayed, with neurons stalling in the intermediate zone and exhibiting an abnormal multipolar morphology. This suggests that RA controls the multipolar-to-bipolar transition that occurs in the intermediate zone and allows neurons to start locomotion in the cortical plate. Our work also shows a role for RA in cortical lamination, as deep layers are expanded and a subset of layer IV neurons are not formed in the Raldh2-ablated mutants. These data demonstrate that meninges are a source of extrinsic signals important for cortical development. The Company of Biologists Ltd 2016-12-23 /pmc/articles/PMC5312094/ /pubmed/28011626 http://dx.doi.org/10.1242/bio.021063 Text en © 2017. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Haushalter, Carole Schuhbaur, Brigitte Dollé, Pascal Rhinn, Muriel Meningeal retinoic acid contributes to neocortical lamination and radial migration during mouse brain development |
title | Meningeal retinoic acid contributes to neocortical lamination and radial migration during mouse brain development |
title_full | Meningeal retinoic acid contributes to neocortical lamination and radial migration during mouse brain development |
title_fullStr | Meningeal retinoic acid contributes to neocortical lamination and radial migration during mouse brain development |
title_full_unstemmed | Meningeal retinoic acid contributes to neocortical lamination and radial migration during mouse brain development |
title_short | Meningeal retinoic acid contributes to neocortical lamination and radial migration during mouse brain development |
title_sort | meningeal retinoic acid contributes to neocortical lamination and radial migration during mouse brain development |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312094/ https://www.ncbi.nlm.nih.gov/pubmed/28011626 http://dx.doi.org/10.1242/bio.021063 |
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