Loss of floor plate Netrin-1 impairs midline crossing of corticospinal axons and leads to mirror movements

In humans, execution of unimanual movements requires lateralized activation of the primary motor cortex, which then transmits the motor command to the contralateral hand through the crossed corticospinal tract (CST). Mutations in NTN1 alter motor control lateralization, leading to congenital mirror...

ver descrição completa

Detalhes bibliográficos
Autores: Pourchet, Oriane, Morel, Marie-Pierre, Welniarz, Quentin, Sarrazin, Nadège, Marti, Fabio, Heck, Nicolas, Galléa, Cécile, Doulazmi, Mohamed, Roig-Puiggros, Sergi, Moreno-Bravo, Juan Antonio, Vidailhet, Marie, Trembleau, Alain, Faure, Philippe, Chédotal, Alain, Roze, Emmanuel, Dusart, Isabelle
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2021
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/308989
Acesso em linha:http://hdl.handle.net/10261/308989
Access Level:Acceso aberto
Palavra-chave:Brain development
Motor control
Neural circuit development
id ES_5a5cbf009e40f9cd00ed397ac9250d13
oai_identifier_str oai:digital.csic.es:10261/308989
network_acronym_str ES
network_name_str España
repository_id_str
spelling Loss of floor plate Netrin-1 impairs midline crossing of corticospinal axons and leads to mirror movementsPourchet, OrianeMorel, Marie-PierreWelniarz, QuentinSarrazin, NadègeMarti, FabioHeck, NicolasGalléa, CécileDoulazmi, MohamedRoig-Puiggros, SergiMoreno-Bravo, Juan AntonioVidailhet, MarieTrembleau, AlainFaure, PhilippeChédotal, AlainRoze, EmmanuelDusart, IsabelleBrain developmentMotor controlNeural circuit developmentIn humans, execution of unimanual movements requires lateralized activation of the primary motor cortex, which then transmits the motor command to the contralateral hand through the crossed corticospinal tract (CST). Mutations in NTN1 alter motor control lateralization, leading to congenital mirror movements. To address the role of midline Netrin-1 on CST development and subsequent motor control, we analyze the morphological and functional consequences of floor plate Netrin-1 depletion in conditional knockout mice. We show that depletion of floor plate Netrin-1 in the brainstem critically disrupts CST midline crossing, whereas the other commissural systems are preserved. The only associated defect is an abnormal entry of CST axons within the inferior olive. Alteration of CST midline crossing results in functional ipsilateral projections and is associated with abnormal symmetric movements. Our study reveals the role of Netrin-1 in CST development and describes a mouse model recapitulating the characteristics of human congenital mirror movements.This work was funded by grant ANR-18-CE16-0005-02 MOMIC, Fondation Desmarest, and Merz Pharma. We also acknowledge Sarujan Devakumaran (IBPS, France) for his contribution to experiments, France Lam for confocal imaging (IBPS, France), Morgane Belle (Institut de la Vision, France) for light-sheet imaging, Alexis Bemelmans (CEA, France) for producing the AAV9-CAG-tdTomato virus, Isabelle Caillé for reviewing the manuscript, and PHENO-ICMice (ICM, France) Core supported by 2 “Investissements d’avenir” (ANR-10- IAIHU-06 and ANR-11-INBS-0011-NeurATRIS), and the “Fondation pour la Recherche Médicale.”Peer reviewedElsevierAgence Nationale de la Recherche (France)Merz PharmaFondation pour la Recherche Médicale202320232021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/308989reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésCell Reportshttps://doi.org/10.1016/j.celrep.2020.108654Noinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3089892026-05-22T06:33:51Z
dc.title.none.fl_str_mv Loss of floor plate Netrin-1 impairs midline crossing of corticospinal axons and leads to mirror movements
title Loss of floor plate Netrin-1 impairs midline crossing of corticospinal axons and leads to mirror movements
spellingShingle Loss of floor plate Netrin-1 impairs midline crossing of corticospinal axons and leads to mirror movements
Pourchet, Oriane
Brain development
Motor control
Neural circuit development
title_short Loss of floor plate Netrin-1 impairs midline crossing of corticospinal axons and leads to mirror movements
title_full Loss of floor plate Netrin-1 impairs midline crossing of corticospinal axons and leads to mirror movements
title_fullStr Loss of floor plate Netrin-1 impairs midline crossing of corticospinal axons and leads to mirror movements
title_full_unstemmed Loss of floor plate Netrin-1 impairs midline crossing of corticospinal axons and leads to mirror movements
title_sort Loss of floor plate Netrin-1 impairs midline crossing of corticospinal axons and leads to mirror movements
dc.creator.none.fl_str_mv Pourchet, Oriane
Morel, Marie-Pierre
Welniarz, Quentin
Sarrazin, Nadège
Marti, Fabio
Heck, Nicolas
Galléa, Cécile
Doulazmi, Mohamed
Roig-Puiggros, Sergi
Moreno-Bravo, Juan Antonio
Vidailhet, Marie
Trembleau, Alain
Faure, Philippe
Chédotal, Alain
Roze, Emmanuel
Dusart, Isabelle
author Pourchet, Oriane
author_facet Pourchet, Oriane
Morel, Marie-Pierre
Welniarz, Quentin
Sarrazin, Nadège
Marti, Fabio
Heck, Nicolas
Galléa, Cécile
Doulazmi, Mohamed
Roig-Puiggros, Sergi
Moreno-Bravo, Juan Antonio
Vidailhet, Marie
Trembleau, Alain
Faure, Philippe
Chédotal, Alain
Roze, Emmanuel
Dusart, Isabelle
author_role author
author2 Morel, Marie-Pierre
Welniarz, Quentin
Sarrazin, Nadège
Marti, Fabio
Heck, Nicolas
Galléa, Cécile
Doulazmi, Mohamed
Roig-Puiggros, Sergi
Moreno-Bravo, Juan Antonio
Vidailhet, Marie
Trembleau, Alain
Faure, Philippe
Chédotal, Alain
Roze, Emmanuel
Dusart, Isabelle
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Agence Nationale de la Recherche (France)
Merz Pharma
Fondation pour la Recherche Médicale
dc.subject.none.fl_str_mv Brain development
Motor control
Neural circuit development
topic Brain development
Motor control
Neural circuit development
description In humans, execution of unimanual movements requires lateralized activation of the primary motor cortex, which then transmits the motor command to the contralateral hand through the crossed corticospinal tract (CST). Mutations in NTN1 alter motor control lateralization, leading to congenital mirror movements. To address the role of midline Netrin-1 on CST development and subsequent motor control, we analyze the morphological and functional consequences of floor plate Netrin-1 depletion in conditional knockout mice. We show that depletion of floor plate Netrin-1 in the brainstem critically disrupts CST midline crossing, whereas the other commissural systems are preserved. The only associated defect is an abnormal entry of CST axons within the inferior olive. Alteration of CST midline crossing results in functional ipsilateral projections and is associated with abnormal symmetric movements. Our study reveals the role of Netrin-1 in CST development and describes a mouse model recapitulating the characteristics of human congenital mirror movements.
publishDate 2021
dc.date.none.fl_str_mv 2021
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/10261/308989
url http://hdl.handle.net/10261/308989
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Cell Reports
https://doi.org/10.1016/j.celrep.2020.108654
No
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 Elsevier
publisher.none.fl_str_mv Elsevier
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_ 1869408691359318016
score 15.812455

Registros relacionados