p73 deficiency results in impaired self renewal and premature neuronal differentiation of mouse neural progenitors independently of p53

10 p.-5 fig.

Detalhes bibliográficos
Autores: González-Cano, L., Herreros-Villanueva, M., Fernández-Alonso, R., Ayuso-Sacido, A., Meyer, Gundela, García-Verdugo, J. M., Silva, Augusto, Marques, M. M., Marín, M. Carmen
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2010
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/103838
Acesso em linha:http://hdl.handle.net/10261/103838
Access Level:Acceso aberto
Palavra-chave:Differentiation
Neural stem cells
p73
p53
Self-renewal
asymmetric division
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spelling p73 deficiency results in impaired self renewal and premature neuronal differentiation of mouse neural progenitors independently of p53González-Cano, L.Herreros-Villanueva, M.Fernández-Alonso, R.Ayuso-Sacido, A.Meyer, GundelaGarcía-Verdugo, J. M.Silva, AugustoMarques, M. M.Marín, M. CarmenDifferentiationNeural stem cellsp73p53Self-renewalasymmetric division10 p.-5 fig.The question of how neural progenitor cells maintain its self-renewal throughout life is a fundamental problem in cell biology with implications in cancer, aging and neurodegenerative diseases. In this work, we have analyzed the p73 function in embryonic neural progenitor cell biology using the neurosphere (NS)-assay and showed that p73-loss has a significant role in the maintenance of neurosphere-forming cells in the embryonic brain. A comparative study of NS from Trp73-/-, p53KO, p53KO;Trp73-/-and their wild-type counterparts demonstrated that p73 deficiency results in two independent, but related, phenotypes: a smaller NS size (related to the proliferation and survival of the neural-progenitors) and a decreased capacity to form NS (self-renewal). The former seems to be the result of p53 compensatory activity, whereas the latter is p53 independent. We also demonstrate that p73 deficiency increases the population of neuronal progenitors ready to differentiate into neurons at the expense of depleting the pool of undifferentiated neurosphere-forming cells. Analysis of the neurogenic niches demonstrated that p73-loss depletes the number of neural-progenitor cells, rendering deficient niches in the adult mice. Altogether, our study identifies TP73 as a positive regulator of self-renewal with a role in the maintenance of the neurogenic capacity. Thus, proposing p73 as an important player in the development of neurodegenerative diseases and a potential therapeutic target.This work was supported by Grants SAF2009- 07897 from Spanish Ministerio de Ciencia e Innovacion (to MCM), Grant from Cajas de Ahorro de Castilla y León (to MCM), and Grants LE030A07 (to MMM) and LE015A10-2 (to MCM) from the Junta de Castilla y León.Peer reviewedNature Publishing GroupConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201420142010info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/103838reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1038/cddis.2010.87Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1038382026-05-22T06:33:51Z
dc.title.none.fl_str_mv p73 deficiency results in impaired self renewal and premature neuronal differentiation of mouse neural progenitors independently of p53
title p73 deficiency results in impaired self renewal and premature neuronal differentiation of mouse neural progenitors independently of p53
spellingShingle p73 deficiency results in impaired self renewal and premature neuronal differentiation of mouse neural progenitors independently of p53
González-Cano, L.
Differentiation
Neural stem cells
p73
p53
Self-renewal
asymmetric division
title_short p73 deficiency results in impaired self renewal and premature neuronal differentiation of mouse neural progenitors independently of p53
title_full p73 deficiency results in impaired self renewal and premature neuronal differentiation of mouse neural progenitors independently of p53
title_fullStr p73 deficiency results in impaired self renewal and premature neuronal differentiation of mouse neural progenitors independently of p53
title_full_unstemmed p73 deficiency results in impaired self renewal and premature neuronal differentiation of mouse neural progenitors independently of p53
title_sort p73 deficiency results in impaired self renewal and premature neuronal differentiation of mouse neural progenitors independently of p53
dc.creator.none.fl_str_mv González-Cano, L.
Herreros-Villanueva, M.
Fernández-Alonso, R.
Ayuso-Sacido, A.
Meyer, Gundela
García-Verdugo, J. M.
Silva, Augusto
Marques, M. M.
Marín, M. Carmen
author González-Cano, L.
author_facet González-Cano, L.
Herreros-Villanueva, M.
Fernández-Alonso, R.
Ayuso-Sacido, A.
Meyer, Gundela
García-Verdugo, J. M.
Silva, Augusto
Marques, M. M.
Marín, M. Carmen
author_role author
author2 Herreros-Villanueva, M.
Fernández-Alonso, R.
Ayuso-Sacido, A.
Meyer, Gundela
García-Verdugo, J. M.
Silva, Augusto
Marques, M. M.
Marín, M. Carmen
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Differentiation
Neural stem cells
p73
p53
Self-renewal
asymmetric division
topic Differentiation
Neural stem cells
p73
p53
Self-renewal
asymmetric division
description 10 p.-5 fig.
publishDate 2010
dc.date.none.fl_str_mv 2010
2014
2014
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/10261/103838
url http://hdl.handle.net/10261/103838
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1038/cddis.2010.87
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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 15.812429

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