GDNF/GFRα1 Complex Abrogates Self-Renewing Activity of Cortical Neural Precursors Inducing Their Differentiation

Autores
Bonafina, Antonela; Fontanet, Paula Aldana; Paratcha, Gustavo; Ledda, Maria Fernanda
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The balance between factors leading to proliferation and differentiation of cortical neural precursors (CNPs) determines the correct cortical development. In this work, we show that GDNF and its receptor GFRα1 are expressed in the neocortex during the period of cortical neurogenesis. We show that the GDNF/GFRα1 complex inhibits the self-renewal capacity of mouse CNP cells induced by fibroblast growth factor 2 (FGF2), promoting neuronal differentiation. While GDNF leads to decreased proliferation of cultured cortical precursor cells, ablation of GFRα1 in glutamatergic cortical precursors enhances its proliferation. We show that GDNF treatment of CNPs promoted morphological differentiation even in the presence of the self-renewal-promoting factor, FGF2. Analysis of GFRα1-deficient mice shows an increase in the number of cycling cells during cortical development and a reduction in dendrite development of cortical GFRα1-expressing neurons. Together, these results indicate that GDNF/GFRα1 signaling plays an essential role in regulating the proliferative condition and the differentiation of cortical progenitors. In this article, Ledda and colleagues show that GDNF acting through its receptor GFRα1 plays a critical role in the maturation of cortical progenitors by counteracting FGF2 self-renewal activity on neural stem cells and promoting neuronal differentiation.
Fil: Bonafina, Antonela. 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 Aldana. 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
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
Materia
CORTICAL PRECURSORS
GDNF
GFRΑ1
NEURONAL DIFFERENTIATION
POSTMITOTIC NEURONS
PROLIFERATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/90065
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/90065
network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling GDNF/GFRα1 Complex Abrogates Self-Renewing Activity of Cortical Neural Precursors Inducing Their DifferentiationBonafina, AntonelaFontanet, Paula AldanaParatcha, GustavoLedda, Maria FernandaCORTICAL PRECURSORSGDNFGFRΑ1NEURONAL DIFFERENTIATIONPOSTMITOTIC NEURONSPROLIFERATIONhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The balance between factors leading to proliferation and differentiation of cortical neural precursors (CNPs) determines the correct cortical development. In this work, we show that GDNF and its receptor GFRα1 are expressed in the neocortex during the period of cortical neurogenesis. We show that the GDNF/GFRα1 complex inhibits the self-renewal capacity of mouse CNP cells induced by fibroblast growth factor 2 (FGF2), promoting neuronal differentiation. While GDNF leads to decreased proliferation of cultured cortical precursor cells, ablation of GFRα1 in glutamatergic cortical precursors enhances its proliferation. We show that GDNF treatment of CNPs promoted morphological differentiation even in the presence of the self-renewal-promoting factor, FGF2. Analysis of GFRα1-deficient mice shows an increase in the number of cycling cells during cortical development and a reduction in dendrite development of cortical GFRα1-expressing neurons. Together, these results indicate that GDNF/GFRα1 signaling plays an essential role in regulating the proliferative condition and the differentiation of cortical progenitors. In this article, Ledda and colleagues show that GDNF acting through its receptor GFRα1 plays a critical role in the maturation of cortical progenitors by counteracting FGF2 self-renewal activity on neural stem cells and promoting neuronal differentiation.Fil: Bonafina, Antonela. 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 Aldana. 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; ArgentinaFil: 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; ArgentinaCell Press2018-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/90065Bonafina, Antonela; Fontanet, Paula Aldana; Paratcha, Gustavo; Ledda, Maria Fernanda; GDNF/GFRα1 Complex Abrogates Self-Renewing Activity of Cortical Neural Precursors Inducing Their Differentiation; Cell Press; Stem Cell Reports; 10; 3; 3-2018; 1000-10152213-6711CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://linkinghub.elsevier.com/retrieve/pii/S2213671118300456info:eu-repo/semantics/altIdentifier/doi/10.1016/j.stemcr.2018.01.019info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T11:29:48Zoai:ri.conicet.gov.ar:11336/90065instacron: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:34982025-09-17 11:29:48.605CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv GDNF/GFRα1 Complex Abrogates Self-Renewing Activity of Cortical Neural Precursors Inducing Their Differentiation
title GDNF/GFRα1 Complex Abrogates Self-Renewing Activity of Cortical Neural Precursors Inducing Their Differentiation
spellingShingle GDNF/GFRα1 Complex Abrogates Self-Renewing Activity of Cortical Neural Precursors Inducing Their Differentiation
Bonafina, Antonela
CORTICAL PRECURSORS
GDNF
GFRΑ1
NEURONAL DIFFERENTIATION
POSTMITOTIC NEURONS
PROLIFERATION
title_short GDNF/GFRα1 Complex Abrogates Self-Renewing Activity of Cortical Neural Precursors Inducing Their Differentiation
title_full GDNF/GFRα1 Complex Abrogates Self-Renewing Activity of Cortical Neural Precursors Inducing Their Differentiation
title_fullStr GDNF/GFRα1 Complex Abrogates Self-Renewing Activity of Cortical Neural Precursors Inducing Their Differentiation
title_full_unstemmed GDNF/GFRα1 Complex Abrogates Self-Renewing Activity of Cortical Neural Precursors Inducing Their Differentiation
title_sort GDNF/GFRα1 Complex Abrogates Self-Renewing Activity of Cortical Neural Precursors Inducing Their Differentiation
dc.creator.none.fl_str_mv Bonafina, Antonela
Fontanet, Paula Aldana
Paratcha, Gustavo
Ledda, Maria Fernanda
author Bonafina, Antonela
author_facet Bonafina, Antonela
Fontanet, Paula Aldana
Paratcha, Gustavo
Ledda, Maria Fernanda
author_role author
author2 Fontanet, Paula Aldana
Paratcha, Gustavo
Ledda, Maria Fernanda
author2_role author
author
author
dc.subject.none.fl_str_mv CORTICAL PRECURSORS
GDNF
GFRΑ1
NEURONAL DIFFERENTIATION
POSTMITOTIC NEURONS
PROLIFERATION
topic CORTICAL PRECURSORS
GDNF
GFRΑ1
NEURONAL DIFFERENTIATION
POSTMITOTIC NEURONS
PROLIFERATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The balance between factors leading to proliferation and differentiation of cortical neural precursors (CNPs) determines the correct cortical development. In this work, we show that GDNF and its receptor GFRα1 are expressed in the neocortex during the period of cortical neurogenesis. We show that the GDNF/GFRα1 complex inhibits the self-renewal capacity of mouse CNP cells induced by fibroblast growth factor 2 (FGF2), promoting neuronal differentiation. While GDNF leads to decreased proliferation of cultured cortical precursor cells, ablation of GFRα1 in glutamatergic cortical precursors enhances its proliferation. We show that GDNF treatment of CNPs promoted morphological differentiation even in the presence of the self-renewal-promoting factor, FGF2. Analysis of GFRα1-deficient mice shows an increase in the number of cycling cells during cortical development and a reduction in dendrite development of cortical GFRα1-expressing neurons. Together, these results indicate that GDNF/GFRα1 signaling plays an essential role in regulating the proliferative condition and the differentiation of cortical progenitors. In this article, Ledda and colleagues show that GDNF acting through its receptor GFRα1 plays a critical role in the maturation of cortical progenitors by counteracting FGF2 self-renewal activity on neural stem cells and promoting neuronal differentiation.
Fil: Bonafina, Antonela. 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 Aldana. 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
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
description The balance between factors leading to proliferation and differentiation of cortical neural precursors (CNPs) determines the correct cortical development. In this work, we show that GDNF and its receptor GFRα1 are expressed in the neocortex during the period of cortical neurogenesis. We show that the GDNF/GFRα1 complex inhibits the self-renewal capacity of mouse CNP cells induced by fibroblast growth factor 2 (FGF2), promoting neuronal differentiation. While GDNF leads to decreased proliferation of cultured cortical precursor cells, ablation of GFRα1 in glutamatergic cortical precursors enhances its proliferation. We show that GDNF treatment of CNPs promoted morphological differentiation even in the presence of the self-renewal-promoting factor, FGF2. Analysis of GFRα1-deficient mice shows an increase in the number of cycling cells during cortical development and a reduction in dendrite development of cortical GFRα1-expressing neurons. Together, these results indicate that GDNF/GFRα1 signaling plays an essential role in regulating the proliferative condition and the differentiation of cortical progenitors. In this article, Ledda and colleagues show that GDNF acting through its receptor GFRα1 plays a critical role in the maturation of cortical progenitors by counteracting FGF2 self-renewal activity on neural stem cells and promoting neuronal differentiation.
publishDate 2018
dc.date.none.fl_str_mv 2018-03
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/11336/90065
Bonafina, Antonela; Fontanet, Paula Aldana; Paratcha, Gustavo; Ledda, Maria Fernanda; GDNF/GFRα1 Complex Abrogates Self-Renewing Activity of Cortical Neural Precursors Inducing Their Differentiation; Cell Press; Stem Cell Reports; 10; 3; 3-2018; 1000-1015
2213-6711
CONICET Digital
CONICET
url http://hdl.handle.net/11336/90065
identifier_str_mv Bonafina, Antonela; Fontanet, Paula Aldana; Paratcha, Gustavo; Ledda, Maria Fernanda; GDNF/GFRα1 Complex Abrogates Self-Renewing Activity of Cortical Neural Precursors Inducing Their Differentiation; Cell Press; Stem Cell Reports; 10; 3; 3-2018; 1000-1015
2213-6711
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://linkinghub.elsevier.com/retrieve/pii/S2213671118300456
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.stemcr.2018.01.019
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
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 13.001348

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