Neuronal LRP4 regulates synapse formation in the developing CNS

The low-density lipoprotein receptor-related protein 4 (LRP4) is essential in muscle fibers for the establishment of the neuromuscular junction. Here, we show that LRP4 is also expressed by embryonic cortical and hippocampal neurons, and that downregulation of LRP4 in these neurons causes a reductio...

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Detalles Bibliográficos
Autores: Karakatsani, Andromachi, Marichal, Nicolás, Urban, Severino, Kalamakis, Georgios, Ghanem, Alexander, Schick, Anna, Zhang, Yina, Conzelmann, Karl-Klaus, Rüegg, Markus A, Berninger, Benedikt, Ruiz de Almodovar, Carmen, Gascón, Sergio, Kröger, Stephan
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/346462
Acceso en línea:http://hdl.handle.net/10261/346462
https://api.elsevier.com/content/abstract/scopus_id/85038440776
Access Level:acceso abierto
Palabra clave:Agrin
Bassoon
Central nervous system development
Dendritogenesis
In utero electroporation
LRP4
Mouse
PSD95
Synapse formation
Transsynaptic tracing
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spelling Neuronal LRP4 regulates synapse formation in the developing CNSKarakatsani, AndromachiMarichal, NicolásUrban, SeverinoKalamakis, GeorgiosGhanem, AlexanderSchick, AnnaZhang, YinaConzelmann, Karl-KlausRüegg, Markus ABerninger, BenediktRuiz de Almodovar, CarmenGascón, SergioKröger, StephanAgrinBassoonCentral nervous system developmentDendritogenesisIn utero electroporationLRP4MousePSD95Synapse formationTranssynaptic tracingThe low-density lipoprotein receptor-related protein 4 (LRP4) is essential in muscle fibers for the establishment of the neuromuscular junction. Here, we show that LRP4 is also expressed by embryonic cortical and hippocampal neurons, and that downregulation of LRP4 in these neurons causes a reduction in density of synapses and number of primary dendrites. Accordingly, overexpression of LRP4 in cultured neurons had the opposite effect inducing more but shorter primary dendrites with an increased number of spines. Transsynaptic tracing mediated by rabies virus revealed a reduced number of neurons presynaptic to the cortical neurons in which LRP4 was knocked down. Moreover, neuron-specific knockdown of LRP4 by in utero electroporation of LRP4 miRNA in vivo also resulted in neurons with fewer primary dendrites and a lower density of spines in the developing cortex and hippocampus. Collectively, our results demonstrate an essential and novel role of neuronal LRP4 in dendritic development and synaptogenesis in the CNS.The work was supported by grants from the Deutsche Forschungsgemeinschaft (DFG; KR1039-11-1 to S.K., SFB870 to A.G. and K.-K.C., and CRC1080 to B.B.) and the European Research Council (ERC-StG-311367 to C.R.A.). N.M. was supported by a Long-Term Fellowship of the Human Frontier Science Program.Peer reviewedCompany of BiologistsGerman Research FoundationEuropean CommissionHuman Frontier Science Program0000-0002-4626-1690#NODATA##NODATA##NODATA##NODATA##NODATA##NODATA##NODATA##NODATA##NODATA##NODATA#0000-0001-8756-7082#NODATA#Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242017info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/346462https://api.elsevier.com/content/abstract/scopus_id/85038440776reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/EC/ERC-StG-311367/Development (Cambridge, England)https://journals.biologists.com/dev/article/144/24/4604/48233/Neuronal-LRP4-regulates-synapse-formation-in-theSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3464622026-05-22T06:33:51Z
dc.title.none.fl_str_mv Neuronal LRP4 regulates synapse formation in the developing CNS
title Neuronal LRP4 regulates synapse formation in the developing CNS
spellingShingle Neuronal LRP4 regulates synapse formation in the developing CNS
Karakatsani, Andromachi
Agrin
Bassoon
Central nervous system development
Dendritogenesis
In utero electroporation
LRP4
Mouse
PSD95
Synapse formation
Transsynaptic tracing
title_short Neuronal LRP4 regulates synapse formation in the developing CNS
title_full Neuronal LRP4 regulates synapse formation in the developing CNS
title_fullStr Neuronal LRP4 regulates synapse formation in the developing CNS
title_full_unstemmed Neuronal LRP4 regulates synapse formation in the developing CNS
title_sort Neuronal LRP4 regulates synapse formation in the developing CNS
dc.creator.none.fl_str_mv Karakatsani, Andromachi
Marichal, Nicolás
Urban, Severino
Kalamakis, Georgios
Ghanem, Alexander
Schick, Anna
Zhang, Yina
Conzelmann, Karl-Klaus
Rüegg, Markus A
Berninger, Benedikt
Ruiz de Almodovar, Carmen
Gascón, Sergio
Kröger, Stephan
author Karakatsani, Andromachi
author_facet Karakatsani, Andromachi
Marichal, Nicolás
Urban, Severino
Kalamakis, Georgios
Ghanem, Alexander
Schick, Anna
Zhang, Yina
Conzelmann, Karl-Klaus
Rüegg, Markus A
Berninger, Benedikt
Ruiz de Almodovar, Carmen
Gascón, Sergio
Kröger, Stephan
author_role author
author2 Marichal, Nicolás
Urban, Severino
Kalamakis, Georgios
Ghanem, Alexander
Schick, Anna
Zhang, Yina
Conzelmann, Karl-Klaus
Rüegg, Markus A
Berninger, Benedikt
Ruiz de Almodovar, Carmen
Gascón, Sergio
Kröger, Stephan
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv German Research Foundation
European Commission
Human Frontier Science Program
0000-0002-4626-1690
#NODATA#
#NODATA#
#NODATA#
#NODATA#
#NODATA#
#NODATA#
#NODATA#
#NODATA#
#NODATA#
#NODATA#
0000-0001-8756-7082
#NODATA#
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Agrin
Bassoon
Central nervous system development
Dendritogenesis
In utero electroporation
LRP4
Mouse
PSD95
Synapse formation
Transsynaptic tracing
topic Agrin
Bassoon
Central nervous system development
Dendritogenesis
In utero electroporation
LRP4
Mouse
PSD95
Synapse formation
Transsynaptic tracing
description The low-density lipoprotein receptor-related protein 4 (LRP4) is essential in muscle fibers for the establishment of the neuromuscular junction. Here, we show that LRP4 is also expressed by embryonic cortical and hippocampal neurons, and that downregulation of LRP4 in these neurons causes a reduction in density of synapses and number of primary dendrites. Accordingly, overexpression of LRP4 in cultured neurons had the opposite effect inducing more but shorter primary dendrites with an increased number of spines. Transsynaptic tracing mediated by rabies virus revealed a reduced number of neurons presynaptic to the cortical neurons in which LRP4 was knocked down. Moreover, neuron-specific knockdown of LRP4 by in utero electroporation of LRP4 miRNA in vivo also resulted in neurons with fewer primary dendrites and a lower density of spines in the developing cortex and hippocampus. Collectively, our results demonstrate an essential and novel role of neuronal LRP4 in dendritic development and synaptogenesis in the CNS.
publishDate 2017
dc.date.none.fl_str_mv 2017
2024
2024
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/10261/346462
https://api.elsevier.com/content/abstract/scopus_id/85038440776
url http://hdl.handle.net/10261/346462
https://api.elsevier.com/content/abstract/scopus_id/85038440776
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/EC/ERC-StG-311367/
Development (Cambridge, England)
https://journals.biologists.com/dev/article/144/24/4604/48233/Neuronal-LRP4-regulates-synapse-formation-in-the
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
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
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score 15,81155

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