Sara regulates neuronal migration during neocortical development through L1 trafficking

Autores
Mestres Lascano, Ivan; Chuang, Jen-Zen; Calegari, Federico; Conde, Cecilia Beatriz; Sung, Ching-Hwa
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Emerging evidence suggests that endocytic trafficking of adhesion proteins plays a crucial role in neuronal migration during neocortical development. However, molecular insights into these processes remain elusive. Here, we study the early endosomal protein Smad anchor for receptor activation (SARA) in the developing mouse brain. SARA is enriched at the apical endfeet of radial glia of the neocortex. Although SARA knockdown did not lead to detectable neurogenic phenotypes, SARA-suppressed neurons exhibited impaired orientation and migration across the intermediate zone. Mechanistically, we show that SARA knockdown neurons exhibit increased surface expression of the L1 cell adhesion molecule. Neurons ectopically expressing L1 phenocopy the migration and orientation defects caused by SARA knockdown and display increased contact with neighboring neurites. L1 knockdown effectively rescues SARA suppressioninduced phenotypes. SARA knockdown neurons eventually overcome their migration defect and enter later into the cortical plate. Nevertheless, these neurons localize at more superficial cortical layers than their control counterparts. These results suggest that SARA regulates the orientation, multipolar-to-bipolar transition and the positioning of cortical neurons via modulating surface L1 expression.
Fil: Mestres Lascano, Ivan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Chuang, Jen-Zen. Cornell University; Estados Unidos
Fil: Calegari, Federico. Dfg-research Center For Regenerative Therapies; Alemania
Fil: Conde, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Sung, Ching-Hwa. Cornell University; Estados Unidos
Materia
Adhesion
Cortical Neuron Migration
Endosomal Trafficking
L1cam
Sara
Zfyve9
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:11336/76546
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/76546
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Sara regulates neuronal migration during neocortical development through L1 traffickingMestres Lascano, IvanChuang, Jen-ZenCalegari, FedericoConde, Cecilia BeatrizSung, Ching-HwaAdhesionCortical Neuron MigrationEndosomal TraffickingL1camSaraZfyve9https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Emerging evidence suggests that endocytic trafficking of adhesion proteins plays a crucial role in neuronal migration during neocortical development. However, molecular insights into these processes remain elusive. Here, we study the early endosomal protein Smad anchor for receptor activation (SARA) in the developing mouse brain. SARA is enriched at the apical endfeet of radial glia of the neocortex. Although SARA knockdown did not lead to detectable neurogenic phenotypes, SARA-suppressed neurons exhibited impaired orientation and migration across the intermediate zone. Mechanistically, we show that SARA knockdown neurons exhibit increased surface expression of the L1 cell adhesion molecule. Neurons ectopically expressing L1 phenocopy the migration and orientation defects caused by SARA knockdown and display increased contact with neighboring neurites. L1 knockdown effectively rescues SARA suppressioninduced phenotypes. SARA knockdown neurons eventually overcome their migration defect and enter later into the cortical plate. Nevertheless, these neurons localize at more superficial cortical layers than their control counterparts. These results suggest that SARA regulates the orientation, multipolar-to-bipolar transition and the positioning of cortical neurons via modulating surface L1 expression.Fil: Mestres Lascano, Ivan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Chuang, Jen-Zen. Cornell University; Estados UnidosFil: Calegari, Federico. Dfg-research Center For Regenerative Therapies; AlemaniaFil: Conde, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Sung, Ching-Hwa. Cornell University; Estados UnidosCompany of Biologists2016-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/76546Mestres Lascano, Ivan; Chuang, Jen-Zen; Calegari, Federico; Conde, Cecilia Beatriz; Sung, Ching-Hwa; Sara regulates neuronal migration during neocortical development through L1 trafficking; Company of Biologists; Development; 143; 17; 9-2016; 3143-31530950-19911477-9129CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/27471254info:eu-repo/semantics/altIdentifier/doi/10.1242/dev.129338info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:19:09Zoai:ri.conicet.gov.ar:11336/76546instacron: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:34982025-10-22 11:19:09.603CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Sara regulates neuronal migration during neocortical development through L1 trafficking
title Sara regulates neuronal migration during neocortical development through L1 trafficking
spellingShingle Sara regulates neuronal migration during neocortical development through L1 trafficking
Mestres Lascano, Ivan
Adhesion
Cortical Neuron Migration
Endosomal Trafficking
L1cam
Sara
Zfyve9
title_short Sara regulates neuronal migration during neocortical development through L1 trafficking
title_full Sara regulates neuronal migration during neocortical development through L1 trafficking
title_fullStr Sara regulates neuronal migration during neocortical development through L1 trafficking
title_full_unstemmed Sara regulates neuronal migration during neocortical development through L1 trafficking
title_sort Sara regulates neuronal migration during neocortical development through L1 trafficking
dc.creator.none.fl_str_mv Mestres Lascano, Ivan
Chuang, Jen-Zen
Calegari, Federico
Conde, Cecilia Beatriz
Sung, Ching-Hwa
author Mestres Lascano, Ivan
author_facet Mestres Lascano, Ivan
Chuang, Jen-Zen
Calegari, Federico
Conde, Cecilia Beatriz
Sung, Ching-Hwa
author_role author
author2 Chuang, Jen-Zen
Calegari, Federico
Conde, Cecilia Beatriz
Sung, Ching-Hwa
author2_role author
author
author
author
dc.subject.none.fl_str_mv Adhesion
Cortical Neuron Migration
Endosomal Trafficking
L1cam
Sara
Zfyve9
topic Adhesion
Cortical Neuron Migration
Endosomal Trafficking
L1cam
Sara
Zfyve9
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Emerging evidence suggests that endocytic trafficking of adhesion proteins plays a crucial role in neuronal migration during neocortical development. However, molecular insights into these processes remain elusive. Here, we study the early endosomal protein Smad anchor for receptor activation (SARA) in the developing mouse brain. SARA is enriched at the apical endfeet of radial glia of the neocortex. Although SARA knockdown did not lead to detectable neurogenic phenotypes, SARA-suppressed neurons exhibited impaired orientation and migration across the intermediate zone. Mechanistically, we show that SARA knockdown neurons exhibit increased surface expression of the L1 cell adhesion molecule. Neurons ectopically expressing L1 phenocopy the migration and orientation defects caused by SARA knockdown and display increased contact with neighboring neurites. L1 knockdown effectively rescues SARA suppressioninduced phenotypes. SARA knockdown neurons eventually overcome their migration defect and enter later into the cortical plate. Nevertheless, these neurons localize at more superficial cortical layers than their control counterparts. These results suggest that SARA regulates the orientation, multipolar-to-bipolar transition and the positioning of cortical neurons via modulating surface L1 expression.
Fil: Mestres Lascano, Ivan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Chuang, Jen-Zen. Cornell University; Estados Unidos
Fil: Calegari, Federico. Dfg-research Center For Regenerative Therapies; Alemania
Fil: Conde, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Sung, Ching-Hwa. Cornell University; Estados Unidos
description Emerging evidence suggests that endocytic trafficking of adhesion proteins plays a crucial role in neuronal migration during neocortical development. However, molecular insights into these processes remain elusive. Here, we study the early endosomal protein Smad anchor for receptor activation (SARA) in the developing mouse brain. SARA is enriched at the apical endfeet of radial glia of the neocortex. Although SARA knockdown did not lead to detectable neurogenic phenotypes, SARA-suppressed neurons exhibited impaired orientation and migration across the intermediate zone. Mechanistically, we show that SARA knockdown neurons exhibit increased surface expression of the L1 cell adhesion molecule. Neurons ectopically expressing L1 phenocopy the migration and orientation defects caused by SARA knockdown and display increased contact with neighboring neurites. L1 knockdown effectively rescues SARA suppressioninduced phenotypes. SARA knockdown neurons eventually overcome their migration defect and enter later into the cortical plate. Nevertheless, these neurons localize at more superficial cortical layers than their control counterparts. These results suggest that SARA regulates the orientation, multipolar-to-bipolar transition and the positioning of cortical neurons via modulating surface L1 expression.
publishDate 2016
dc.date.none.fl_str_mv 2016-09
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/11336/76546
Mestres Lascano, Ivan; Chuang, Jen-Zen; Calegari, Federico; Conde, Cecilia Beatriz; Sung, Ching-Hwa; Sara regulates neuronal migration during neocortical development through L1 trafficking; Company of Biologists; Development; 143; 17; 9-2016; 3143-3153
0950-1991
1477-9129
CONICET Digital
CONICET
url http://hdl.handle.net/11336/76546
identifier_str_mv Mestres Lascano, Ivan; Chuang, Jen-Zen; Calegari, Federico; Conde, Cecilia Beatriz; Sung, Ching-Hwa; Sara regulates neuronal migration during neocortical development through L1 trafficking; Company of Biologists; Development; 143; 17; 9-2016; 3143-3153
0950-1991
1477-9129
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/27471254
info:eu-repo/semantics/altIdentifier/doi/10.1242/dev.129338
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
_version_ 1846781664982728704
score 12.982451

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