Lrig1 and lrig3 cooperate to control ret receptor signaling, sensory axonal growth and epidermal innervations

Autores
de Vincenti, Ana Paula; Alsina, Fernando Cruz; Ferrero Restelli, Facundo Nahuel; Hedman, Håkan; Ledda, Maria Fernanda; Paratcha, Gustavo
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Negative feedback loops represent a regulatory mechanism that guarantees that signaling thresholds are compatible with a physiological response. Previously, we established that Lrig1 acts through this mechanism to inhibit Ret activity. However, it is unclear whether other Lrig family members play similar roles. Here, we show that Lrig1 and Lrig3 are co-expressed in Ret-positive mouse dorsal root ganglion (DRG) neurons. Lrig3, like Lrig1, interacts with Ret and inhibits GDNF/Ret signaling. Treatment of DRG neurons with GDNF ligands induces a significant increase in the expression of Lrig1 and Lrig3. Our findings show that, whereas a single deletion of either Lrig1 or Lrig3 fails to promote Ret-mediated axonal growth, haploinsufficiency of Lrig1 in Lrig3 mutants significantly potentiates Ret signaling and axonal growth of DRG neurons in response to GDNF ligands. We observe that Lrig1 and Lrig3 act redundantly to ensure proper cutaneous innervation of nonpeptidergic axons and behavioral sensitivity to cold, which correlates with a significant increase in the expression of the cold-responsive channel TrpA1. Together, our findings provide insights into the in vivo functions through which Lrig genes control morphology, connectivity and function in sensory neurons.
Fil: de Vincenti, Ana 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: 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: Ferrero Restelli, Facundo Nahuel. 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, Håkan. Universidad de Umea; Suecia
Fil: Ledda, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Paratcha, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Materia
CUTANEOUS SENSORY INNERVATION AND NOCICEPTIVE NEURONS
DORSAL ROOT GANGLIA (DRG)
GDNF
GFRA
LRIG FAMILY MEMBERS
MOUSE
RET
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:11336/168527
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/168527
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Lrig1 and lrig3 cooperate to control ret receptor signaling, sensory axonal growth and epidermal innervationsde Vincenti, Ana PaulaAlsina, Fernando CruzFerrero Restelli, Facundo NahuelHedman, HåkanLedda, Maria FernandaParatcha, GustavoCUTANEOUS SENSORY INNERVATION AND NOCICEPTIVE NEURONSDORSAL ROOT GANGLIA (DRG)GDNFGFRALRIG FAMILY MEMBERSMOUSEREThttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Negative feedback loops represent a regulatory mechanism that guarantees that signaling thresholds are compatible with a physiological response. Previously, we established that Lrig1 acts through this mechanism to inhibit Ret activity. However, it is unclear whether other Lrig family members play similar roles. Here, we show that Lrig1 and Lrig3 are co-expressed in Ret-positive mouse dorsal root ganglion (DRG) neurons. Lrig3, like Lrig1, interacts with Ret and inhibits GDNF/Ret signaling. Treatment of DRG neurons with GDNF ligands induces a significant increase in the expression of Lrig1 and Lrig3. Our findings show that, whereas a single deletion of either Lrig1 or Lrig3 fails to promote Ret-mediated axonal growth, haploinsufficiency of Lrig1 in Lrig3 mutants significantly potentiates Ret signaling and axonal growth of DRG neurons in response to GDNF ligands. We observe that Lrig1 and Lrig3 act redundantly to ensure proper cutaneous innervation of nonpeptidergic axons and behavioral sensitivity to cold, which correlates with a significant increase in the expression of the cold-responsive channel TrpA1. Together, our findings provide insights into the in vivo functions through which Lrig genes control morphology, connectivity and function in sensory neurons.Fil: de Vincenti, Ana 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: 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: Ferrero Restelli, Facundo Nahuel. 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, Håkan. Universidad de Umea; SueciaFil: Ledda, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Paratcha, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaCompany of Biologists2021-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/168527de Vincenti, Ana Paula; Alsina, Fernando Cruz; Ferrero Restelli, Facundo Nahuel; Hedman, Håkan; Ledda, Maria Fernanda; et al.; Lrig1 and lrig3 cooperate to control ret receptor signaling, sensory axonal growth and epidermal innervations; Company of Biologists; Development; 148; 18; 8-2021; 1-170950-1991CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1242/dev.197020info:eu-repo/semantics/altIdentifier/url/https://journals.biologists.com/dev/article/148/16/dev197020/271822/Lrig1-and-Lrig3-cooperate-to-control-Ret-receptorinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:01:36Zoai:ri.conicet.gov.ar:11336/168527instacron: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:34982025-09-10 13:01:36.349CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Lrig1 and lrig3 cooperate to control ret receptor signaling, sensory axonal growth and epidermal innervations
title Lrig1 and lrig3 cooperate to control ret receptor signaling, sensory axonal growth and epidermal innervations
spellingShingle Lrig1 and lrig3 cooperate to control ret receptor signaling, sensory axonal growth and epidermal innervations
de Vincenti, Ana Paula
CUTANEOUS SENSORY INNERVATION AND NOCICEPTIVE NEURONS
DORSAL ROOT GANGLIA (DRG)
GDNF
GFRA
LRIG FAMILY MEMBERS
MOUSE
RET
title_short Lrig1 and lrig3 cooperate to control ret receptor signaling, sensory axonal growth and epidermal innervations
title_full Lrig1 and lrig3 cooperate to control ret receptor signaling, sensory axonal growth and epidermal innervations
title_fullStr Lrig1 and lrig3 cooperate to control ret receptor signaling, sensory axonal growth and epidermal innervations
title_full_unstemmed Lrig1 and lrig3 cooperate to control ret receptor signaling, sensory axonal growth and epidermal innervations
title_sort Lrig1 and lrig3 cooperate to control ret receptor signaling, sensory axonal growth and epidermal innervations
dc.creator.none.fl_str_mv de Vincenti, Ana Paula
Alsina, Fernando Cruz
Ferrero Restelli, Facundo Nahuel
Hedman, Håkan
Ledda, Maria Fernanda
Paratcha, Gustavo
author de Vincenti, Ana Paula
author_facet de Vincenti, Ana Paula
Alsina, Fernando Cruz
Ferrero Restelli, Facundo Nahuel
Hedman, Håkan
Ledda, Maria Fernanda
Paratcha, Gustavo
author_role author
author2 Alsina, Fernando Cruz
Ferrero Restelli, Facundo Nahuel
Hedman, Håkan
Ledda, Maria Fernanda
Paratcha, Gustavo
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv CUTANEOUS SENSORY INNERVATION AND NOCICEPTIVE NEURONS
DORSAL ROOT GANGLIA (DRG)
GDNF
GFRA
LRIG FAMILY MEMBERS
MOUSE
RET
topic CUTANEOUS SENSORY INNERVATION AND NOCICEPTIVE NEURONS
DORSAL ROOT GANGLIA (DRG)
GDNF
GFRA
LRIG FAMILY MEMBERS
MOUSE
RET
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Negative feedback loops represent a regulatory mechanism that guarantees that signaling thresholds are compatible with a physiological response. Previously, we established that Lrig1 acts through this mechanism to inhibit Ret activity. However, it is unclear whether other Lrig family members play similar roles. Here, we show that Lrig1 and Lrig3 are co-expressed in Ret-positive mouse dorsal root ganglion (DRG) neurons. Lrig3, like Lrig1, interacts with Ret and inhibits GDNF/Ret signaling. Treatment of DRG neurons with GDNF ligands induces a significant increase in the expression of Lrig1 and Lrig3. Our findings show that, whereas a single deletion of either Lrig1 or Lrig3 fails to promote Ret-mediated axonal growth, haploinsufficiency of Lrig1 in Lrig3 mutants significantly potentiates Ret signaling and axonal growth of DRG neurons in response to GDNF ligands. We observe that Lrig1 and Lrig3 act redundantly to ensure proper cutaneous innervation of nonpeptidergic axons and behavioral sensitivity to cold, which correlates with a significant increase in the expression of the cold-responsive channel TrpA1. Together, our findings provide insights into the in vivo functions through which Lrig genes control morphology, connectivity and function in sensory neurons.
Fil: de Vincenti, Ana 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: 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: Ferrero Restelli, Facundo Nahuel. 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, Håkan. Universidad de Umea; Suecia
Fil: Ledda, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Paratcha, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
description Negative feedback loops represent a regulatory mechanism that guarantees that signaling thresholds are compatible with a physiological response. Previously, we established that Lrig1 acts through this mechanism to inhibit Ret activity. However, it is unclear whether other Lrig family members play similar roles. Here, we show that Lrig1 and Lrig3 are co-expressed in Ret-positive mouse dorsal root ganglion (DRG) neurons. Lrig3, like Lrig1, interacts with Ret and inhibits GDNF/Ret signaling. Treatment of DRG neurons with GDNF ligands induces a significant increase in the expression of Lrig1 and Lrig3. Our findings show that, whereas a single deletion of either Lrig1 or Lrig3 fails to promote Ret-mediated axonal growth, haploinsufficiency of Lrig1 in Lrig3 mutants significantly potentiates Ret signaling and axonal growth of DRG neurons in response to GDNF ligands. We observe that Lrig1 and Lrig3 act redundantly to ensure proper cutaneous innervation of nonpeptidergic axons and behavioral sensitivity to cold, which correlates with a significant increase in the expression of the cold-responsive channel TrpA1. Together, our findings provide insights into the in vivo functions through which Lrig genes control morphology, connectivity and function in sensory neurons.
publishDate 2021
dc.date.none.fl_str_mv 2021-08
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/11336/168527
de Vincenti, Ana Paula; Alsina, Fernando Cruz; Ferrero Restelli, Facundo Nahuel; Hedman, Håkan; Ledda, Maria Fernanda; et al.; Lrig1 and lrig3 cooperate to control ret receptor signaling, sensory axonal growth and epidermal innervations; Company of Biologists; Development; 148; 18; 8-2021; 1-17
0950-1991
CONICET Digital
CONICET
url http://hdl.handle.net/11336/168527
identifier_str_mv de Vincenti, Ana Paula; Alsina, Fernando Cruz; Ferrero Restelli, Facundo Nahuel; Hedman, Håkan; Ledda, Maria Fernanda; et al.; Lrig1 and lrig3 cooperate to control ret receptor signaling, sensory axonal growth and epidermal innervations; Company of Biologists; Development; 148; 18; 8-2021; 1-17
0950-1991
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1242/dev.197020
info:eu-repo/semantics/altIdentifier/url/https://journals.biologists.com/dev/article/148/16/dev197020/271822/Lrig1-and-Lrig3-cooperate-to-control-Ret-receptor
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/
dc.format.none.fl_str_mv application/pdf
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: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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score 12.993085

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