Reelin-dependent ApoER2 downregulation uncouples newborn neurons from progenitor cells

Reelin and its receptor machinery are well known to be required for the migration and positioning of neocortical projection neurons. More recently, reelin has been shown both necessary and sufficient to determine the rate of neocortical neurogenesis. The molecular links underlying its seemingly dist...

Descripción completa

Detalles Bibliográficos
Autores: Pérez-Martínez, F. Javier, Luque-Río, Alvaro, Sakakibara, Akira, Hattori, Mitsuharu, Miyata, Takaki, Luque, Juan M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2012
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/333503
Acceso en línea:http://hdl.handle.net/10261/333503
Access Level:acceso abierto
Palabra clave:Reelin
ApoER2
Dab1
Neurogenesis
Neuronal migration
Mouse
id ES_cfebe9b5271b53b02b66ae87bbb62baa
oai_identifier_str oai:digital.csic.es:10261/333503
network_acronym_str ES
network_name_str España
repository_id_str
spelling Reelin-dependent ApoER2 downregulation uncouples newborn neurons from progenitor cellsPérez-Martínez, F. JavierLuque-Río, AlvaroSakakibara, AkiraHattori, MitsuharuMiyata, TakakiLuque, Juan M.ReelinApoER2Dab1NeurogenesisNeuronal migrationMouseReelin and its receptor machinery are well known to be required for the migration and positioning of neocortical projection neurons. More recently, reelin has been shown both necessary and sufficient to determine the rate of neocortical neurogenesis. The molecular links underlying its seemingly distinct proliferative and post-proliferative functions remain unknown. Here we reveal an enriched expression of functional reelin receptors, largely of Apolipoprotein E Receptor 2 (ApoER2), in radial glia basal processes and intermediate progenitor cells during mid/late cortical development. In vivo, ApoER2 overexpression inhibits neuronal migration. In contrast, precluding excessive levels of ApoER2 in reelin-deficient cortices, by either ApoER2 knock-down or the transgenic expression of reelin in neural progenitor cells, improves neuronal migration and positioning. Our study provides groundwork for the highly orchestrated clearance of neocortical neurons from their birth site, suggesting that a reelin-dependent ApoER2 downregulation mechanism uncouples newborn neurons from progenitor cells, thereby enabling neurons to migrate.F.J.P.-M. held graduate fellowships from the Universidad Miguel Hernandez/Fundacion Medica Mutua Madrileña (FMMM) and the Japan Society for the Promotion of Science (Global COE Program). This work was supported in part by grants from Japanese Grant-in-Aids for Scientific Research on Innovative Area (Neural Diversity and Neocortical Organization), and for Scientific Research (B) [to M.H.]; KAKENHI 20021016 and 22111006 [to T.M.]; the Spanish Ministry of Science and Innovation SAF2004-07685 and the FMMM [to J.M.L.].Peer reviewedCompany of BiologistsUniversidad Miguel HernándezFundación Mutua MadrileñaJapan Society for the Promotion of ScienceMinisterio de Ciencia e Innovación (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202320232012info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/333503reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.1242/bio.20122816Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3335032026-05-22T06:33:51Z
dc.title.none.fl_str_mv Reelin-dependent ApoER2 downregulation uncouples newborn neurons from progenitor cells
title Reelin-dependent ApoER2 downregulation uncouples newborn neurons from progenitor cells
spellingShingle Reelin-dependent ApoER2 downregulation uncouples newborn neurons from progenitor cells
Pérez-Martínez, F. Javier
Reelin
ApoER2
Dab1
Neurogenesis
Neuronal migration
Mouse
title_short Reelin-dependent ApoER2 downregulation uncouples newborn neurons from progenitor cells
title_full Reelin-dependent ApoER2 downregulation uncouples newborn neurons from progenitor cells
title_fullStr Reelin-dependent ApoER2 downregulation uncouples newborn neurons from progenitor cells
title_full_unstemmed Reelin-dependent ApoER2 downregulation uncouples newborn neurons from progenitor cells
title_sort Reelin-dependent ApoER2 downregulation uncouples newborn neurons from progenitor cells
dc.creator.none.fl_str_mv Pérez-Martínez, F. Javier
Luque-Río, Alvaro
Sakakibara, Akira
Hattori, Mitsuharu
Miyata, Takaki
Luque, Juan M.
author Pérez-Martínez, F. Javier
author_facet Pérez-Martínez, F. Javier
Luque-Río, Alvaro
Sakakibara, Akira
Hattori, Mitsuharu
Miyata, Takaki
Luque, Juan M.
author_role author
author2 Luque-Río, Alvaro
Sakakibara, Akira
Hattori, Mitsuharu
Miyata, Takaki
Luque, Juan M.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Miguel Hernández
Fundación Mutua Madrileña
Japan Society for the Promotion of Science
Ministerio de Ciencia e Innovación (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Reelin
ApoER2
Dab1
Neurogenesis
Neuronal migration
Mouse
topic Reelin
ApoER2
Dab1
Neurogenesis
Neuronal migration
Mouse
description Reelin and its receptor machinery are well known to be required for the migration and positioning of neocortical projection neurons. More recently, reelin has been shown both necessary and sufficient to determine the rate of neocortical neurogenesis. The molecular links underlying its seemingly distinct proliferative and post-proliferative functions remain unknown. Here we reveal an enriched expression of functional reelin receptors, largely of Apolipoprotein E Receptor 2 (ApoER2), in radial glia basal processes and intermediate progenitor cells during mid/late cortical development. In vivo, ApoER2 overexpression inhibits neuronal migration. In contrast, precluding excessive levels of ApoER2 in reelin-deficient cortices, by either ApoER2 knock-down or the transgenic expression of reelin in neural progenitor cells, improves neuronal migration and positioning. Our study provides groundwork for the highly orchestrated clearance of neocortical neurons from their birth site, suggesting that a reelin-dependent ApoER2 downregulation mechanism uncouples newborn neurons from progenitor cells, thereby enabling neurons to migrate.
publishDate 2012
dc.date.none.fl_str_mv 2012
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/333503
url http://hdl.handle.net/10261/333503
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.1242/bio.20122816
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Company of Biologists
publisher.none.fl_str_mv Company of Biologists
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869420127142805504
score 15.81155

Similares en LA Referencia