Lrig1 is a cell-intrinsic modulator of hippocampal dendrite complexity and BDNF signaling

Autores
Alsina, Fernando Cruz; Hita, Francisco Javier; Fontanet, Paula; Irala, Dolores; Hedman, Häkan; Ledda, Maria Fernanda; Paratcha, Gustavo
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Even though many extracellular factors have been identified as promoters of general dendritic growth and branching, little is known about the cell-intrinsic modulators that allow neurons to sculpt distinctive patterns of dendrite arborization. Here, we identify Lrig1, a nervous system-enriched LRR protein, as a key physiological regulator of dendrite complexity of hippocampal pyramidal neurons. Lrig1-deficient mice display morphological changes in proximal dendrite arborization and defects in social interaction. Specifically, knockdown of Lrig1 enhances both primary dendrite formation and proximal dendritic branching of hippocampal neurons, two phenotypes that resemble the effect of BDNF on these neurons. In addition, we show that Lrig1 physically interacts with TrkB and attenuates BDNF signaling. Gain and loss of function assays indicate that Lrig1 restricts BDNF-induced dendrite morphology. Together, our findings reveal a novel and essential role of Lrig1 in regulating morphogenic events that shape the hippocampal circuits and establish that the assembly of TrkB with Lrig1 represents a key mechanism for understanding how specific neuronal populations expand the repertoire of responses to BDNF during brain development. Synopsis Lrig1 is a novel regulator of dendritogenesis and apical dendrite branching of CA1-CA3 pyramidal hippocampal neurons in vivo, acting as an endogenous inhibitor of neurotrophin-induced proximal dendrite arborization of pyramidal hippocampal neurons. Lrig1 is a physiological regulator of hippocampal dendrite development. Lrig1 is required for proper apical dendrite arborization of CA1-CA3 pyramidal neurons and social behavior. Lrig1 controls TrkB signaling and dendrite development induced by BDNF. Lrig1 regulates dendritogenesis and apical dendrite branching of CA1-CA3 pyramidal hippocampal neurons in vivo, acting as an endogenous inhibitor of neurotrophin-induced proximal dendrite arborization of pyramidal hippocampal neurons.
Fil: Alsina, Fernando Cruz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Hita, Francisco Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Fontanet, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Irala, Dolores. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Hedman, Häkan. Universidad de Umea; Suecia
Fil: Ledda, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Paratcha, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Materia
Dendrite Morphogenesis
Hippocampal Neurons
Lrig1
Neurotrophins
Trkb
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/39006
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Lrig1 is a cell-intrinsic modulator of hippocampal dendrite complexity and BDNF signalingAlsina, Fernando CruzHita, Francisco JavierFontanet, PaulaIrala, DoloresHedman, HäkanLedda, Maria FernandaParatcha, GustavoDendrite MorphogenesisHippocampal NeuronsLrig1NeurotrophinsTrkbhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Even though many extracellular factors have been identified as promoters of general dendritic growth and branching, little is known about the cell-intrinsic modulators that allow neurons to sculpt distinctive patterns of dendrite arborization. Here, we identify Lrig1, a nervous system-enriched LRR protein, as a key physiological regulator of dendrite complexity of hippocampal pyramidal neurons. Lrig1-deficient mice display morphological changes in proximal dendrite arborization and defects in social interaction. Specifically, knockdown of Lrig1 enhances both primary dendrite formation and proximal dendritic branching of hippocampal neurons, two phenotypes that resemble the effect of BDNF on these neurons. In addition, we show that Lrig1 physically interacts with TrkB and attenuates BDNF signaling. Gain and loss of function assays indicate that Lrig1 restricts BDNF-induced dendrite morphology. Together, our findings reveal a novel and essential role of Lrig1 in regulating morphogenic events that shape the hippocampal circuits and establish that the assembly of TrkB with Lrig1 represents a key mechanism for understanding how specific neuronal populations expand the repertoire of responses to BDNF during brain development. Synopsis Lrig1 is a novel regulator of dendritogenesis and apical dendrite branching of CA1-CA3 pyramidal hippocampal neurons in vivo, acting as an endogenous inhibitor of neurotrophin-induced proximal dendrite arborization of pyramidal hippocampal neurons. Lrig1 is a physiological regulator of hippocampal dendrite development. Lrig1 is required for proper apical dendrite arborization of CA1-CA3 pyramidal neurons and social behavior. Lrig1 controls TrkB signaling and dendrite development induced by BDNF. Lrig1 regulates dendritogenesis and apical dendrite branching of CA1-CA3 pyramidal hippocampal neurons in vivo, acting as an endogenous inhibitor of neurotrophin-induced proximal dendrite arborization of pyramidal hippocampal neurons.Fil: Alsina, Fernando Cruz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Hita, Francisco Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Fontanet, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Irala, Dolores. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Hedman, Häkan. Universidad de Umea; SueciaFil: Ledda, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Paratcha, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaNature Publishing Group2016-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/39006Alsina, Fernando Cruz; Hita, Francisco Javier; Fontanet, Paula; Irala, Dolores; Hedman, Häkan; et al.; Lrig1 is a cell-intrinsic modulator of hippocampal dendrite complexity and BDNF signaling; Nature Publishing Group; Embo Reports; 17; 4; 4-2016; 601-6161469-221XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.15252/embr.201541218info:eu-repo/semantics/altIdentifier/url/http://embor.embopress.org/content/17/4/601info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:38:33Zoai:ri.conicet.gov.ar:11336/39006instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:38:33.353CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Lrig1 is a cell-intrinsic modulator of hippocampal dendrite complexity and BDNF signaling
title Lrig1 is a cell-intrinsic modulator of hippocampal dendrite complexity and BDNF signaling
spellingShingle Lrig1 is a cell-intrinsic modulator of hippocampal dendrite complexity and BDNF signaling
Alsina, Fernando Cruz
Dendrite Morphogenesis
Hippocampal Neurons
Lrig1
Neurotrophins
Trkb
title_short Lrig1 is a cell-intrinsic modulator of hippocampal dendrite complexity and BDNF signaling
title_full Lrig1 is a cell-intrinsic modulator of hippocampal dendrite complexity and BDNF signaling
title_fullStr Lrig1 is a cell-intrinsic modulator of hippocampal dendrite complexity and BDNF signaling
title_full_unstemmed Lrig1 is a cell-intrinsic modulator of hippocampal dendrite complexity and BDNF signaling
title_sort Lrig1 is a cell-intrinsic modulator of hippocampal dendrite complexity and BDNF signaling
dc.creator.none.fl_str_mv Alsina, Fernando Cruz
Hita, Francisco Javier
Fontanet, Paula
Irala, Dolores
Hedman, Häkan
Ledda, Maria Fernanda
Paratcha, Gustavo
author Alsina, Fernando Cruz
author_facet Alsina, Fernando Cruz
Hita, Francisco Javier
Fontanet, Paula
Irala, Dolores
Hedman, Häkan
Ledda, Maria Fernanda
Paratcha, Gustavo
author_role author
author2 Hita, Francisco Javier
Fontanet, Paula
Irala, Dolores
Hedman, Häkan
Ledda, Maria Fernanda
Paratcha, Gustavo
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Dendrite Morphogenesis
Hippocampal Neurons
Lrig1
Neurotrophins
Trkb
topic Dendrite Morphogenesis
Hippocampal Neurons
Lrig1
Neurotrophins
Trkb
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Even though many extracellular factors have been identified as promoters of general dendritic growth and branching, little is known about the cell-intrinsic modulators that allow neurons to sculpt distinctive patterns of dendrite arborization. Here, we identify Lrig1, a nervous system-enriched LRR protein, as a key physiological regulator of dendrite complexity of hippocampal pyramidal neurons. Lrig1-deficient mice display morphological changes in proximal dendrite arborization and defects in social interaction. Specifically, knockdown of Lrig1 enhances both primary dendrite formation and proximal dendritic branching of hippocampal neurons, two phenotypes that resemble the effect of BDNF on these neurons. In addition, we show that Lrig1 physically interacts with TrkB and attenuates BDNF signaling. Gain and loss of function assays indicate that Lrig1 restricts BDNF-induced dendrite morphology. Together, our findings reveal a novel and essential role of Lrig1 in regulating morphogenic events that shape the hippocampal circuits and establish that the assembly of TrkB with Lrig1 represents a key mechanism for understanding how specific neuronal populations expand the repertoire of responses to BDNF during brain development. Synopsis Lrig1 is a novel regulator of dendritogenesis and apical dendrite branching of CA1-CA3 pyramidal hippocampal neurons in vivo, acting as an endogenous inhibitor of neurotrophin-induced proximal dendrite arborization of pyramidal hippocampal neurons. Lrig1 is a physiological regulator of hippocampal dendrite development. Lrig1 is required for proper apical dendrite arborization of CA1-CA3 pyramidal neurons and social behavior. Lrig1 controls TrkB signaling and dendrite development induced by BDNF. Lrig1 regulates dendritogenesis and apical dendrite branching of CA1-CA3 pyramidal hippocampal neurons in vivo, acting as an endogenous inhibitor of neurotrophin-induced proximal dendrite arborization of pyramidal hippocampal neurons.
Fil: Alsina, Fernando Cruz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Hita, Francisco Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Fontanet, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Irala, Dolores. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Hedman, Häkan. Universidad de Umea; Suecia
Fil: Ledda, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Paratcha, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
description Even though many extracellular factors have been identified as promoters of general dendritic growth and branching, little is known about the cell-intrinsic modulators that allow neurons to sculpt distinctive patterns of dendrite arborization. Here, we identify Lrig1, a nervous system-enriched LRR protein, as a key physiological regulator of dendrite complexity of hippocampal pyramidal neurons. Lrig1-deficient mice display morphological changes in proximal dendrite arborization and defects in social interaction. Specifically, knockdown of Lrig1 enhances both primary dendrite formation and proximal dendritic branching of hippocampal neurons, two phenotypes that resemble the effect of BDNF on these neurons. In addition, we show that Lrig1 physically interacts with TrkB and attenuates BDNF signaling. Gain and loss of function assays indicate that Lrig1 restricts BDNF-induced dendrite morphology. Together, our findings reveal a novel and essential role of Lrig1 in regulating morphogenic events that shape the hippocampal circuits and establish that the assembly of TrkB with Lrig1 represents a key mechanism for understanding how specific neuronal populations expand the repertoire of responses to BDNF during brain development. Synopsis Lrig1 is a novel regulator of dendritogenesis and apical dendrite branching of CA1-CA3 pyramidal hippocampal neurons in vivo, acting as an endogenous inhibitor of neurotrophin-induced proximal dendrite arborization of pyramidal hippocampal neurons. Lrig1 is a physiological regulator of hippocampal dendrite development. Lrig1 is required for proper apical dendrite arborization of CA1-CA3 pyramidal neurons and social behavior. Lrig1 controls TrkB signaling and dendrite development induced by BDNF. Lrig1 regulates dendritogenesis and apical dendrite branching of CA1-CA3 pyramidal hippocampal neurons in vivo, acting as an endogenous inhibitor of neurotrophin-induced proximal dendrite arborization of pyramidal hippocampal neurons.
publishDate 2016
dc.date.none.fl_str_mv 2016-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/39006
Alsina, Fernando Cruz; Hita, Francisco Javier; Fontanet, Paula; Irala, Dolores; Hedman, Häkan; et al.; Lrig1 is a cell-intrinsic modulator of hippocampal dendrite complexity and BDNF signaling; Nature Publishing Group; Embo Reports; 17; 4; 4-2016; 601-616
1469-221X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/39006
identifier_str_mv Alsina, Fernando Cruz; Hita, Francisco Javier; Fontanet, Paula; Irala, Dolores; Hedman, Häkan; et al.; Lrig1 is a cell-intrinsic modulator of hippocampal dendrite complexity and BDNF signaling; Nature Publishing Group; Embo Reports; 17; 4; 4-2016; 601-616
1469-221X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/url/http://embor.embopress.org/content/17/4/601
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
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application/pdf
application/pdf
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dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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