MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate Neurogenesis
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.7/700 |
Resumo: | The generation of neurons from neural stem cells requires large-scale changes in gene expression that are controlled to a large extent by proneural transcription factors, such as Ascl1. While recent studies have characterized the differentiation genes activated by proneural factors, less is known on the mechanisms that suppress progenitor cell identity. Here, we show that Ascl1 induces the transcription factor MyT1 while promoting neuronal differentiation. We combined functional studies of MyT1 during neurogenesis with the characterization of its transcriptional program. MyT1 binding is associated with repression of gene transcription in neural progenitor cells. It promotes neuronal differentiation by counteracting the inhibitory activity of Notch signaling at multiple levels, targeting the Notch1 receptor and many of its downstream targets. These include regulators of the neural progenitor program, such as Hes1, Sox2, Id3, and Olig1. Thus, Ascl1 suppresses Notch signaling cell-autonomously via MyT1, coupling neuronal differentiation with repression of the progenitor fate. |
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MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate NeurogenesisAscl1Hes1MyT1Notch signalingRbpjneurogenesistranscriptionThe generation of neurons from neural stem cells requires large-scale changes in gene expression that are controlled to a large extent by proneural transcription factors, such as Ascl1. While recent studies have characterized the differentiation genes activated by proneural factors, less is known on the mechanisms that suppress progenitor cell identity. Here, we show that Ascl1 induces the transcription factor MyT1 while promoting neuronal differentiation. We combined functional studies of MyT1 during neurogenesis with the characterization of its transcriptional program. MyT1 binding is associated with repression of gene transcription in neural progenitor cells. It promotes neuronal differentiation by counteracting the inhibitory activity of Notch signaling at multiple levels, targeting the Notch1 receptor and many of its downstream targets. These include regulators of the neural progenitor program, such as Hes1, Sox2, Id3, and Olig1. Thus, Ascl1 suppresses Notch signaling cell-autonomously via MyT1, coupling neuronal differentiation with repression of the progenitor fate.Fundação para a Ciência e Tecnologia grants: (PTDC/NEU-NMC/031572012, IF/00413/2012); Telethon grant: (GGP15096); Italian Ministry of Health Young investigator grant: (GR-2013-02355540).ElsevierARCAVasconcelos, Francisca F.Sessa, AlessandroLaranjeira, CátiaRaposo, Alexandre A.S.F.Teixeira, VeraHagey, Daniel W.Tomaz, Diogo M.Muhr, JonasBroccoli, VaniaCastro, Diogo S.2016-10-13T14:23:57Z2016-10-042016-10-04T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.7/700engFrancisca F. Vasconcelos, Alessandro Sessa, Cátia Laranjeira, Alexandre A.S.F. Raposo, Vera Teixeira, Daniel W. Hagey, Diogo M. Tomaz, Jonas Muhr, Vania Broccoli, Diogo S. Castro, MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate Neurogenesis, Cell Reports, Volume 17, Issue 2, 4 October 2016, Pages 469-483, ISSN 2211-1247, http://dx.doi.org/10.1016/j.celrep.2016.09.024.10.1016/j.celrep.2016.09.024info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-11-29T14:35:05Zoai:arca.igc.gulbenkian.pt:10400.7/700Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:11:55.957855Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate Neurogenesis |
title |
MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate Neurogenesis |
spellingShingle |
MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate Neurogenesis Vasconcelos, Francisca F. Ascl1 Hes1 MyT1 Notch signaling Rbpj neurogenesis transcription |
title_short |
MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate Neurogenesis |
title_full |
MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate Neurogenesis |
title_fullStr |
MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate Neurogenesis |
title_full_unstemmed |
MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate Neurogenesis |
title_sort |
MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate Neurogenesis |
author |
Vasconcelos, Francisca F. |
author_facet |
Vasconcelos, Francisca F. Sessa, Alessandro Laranjeira, Cátia Raposo, Alexandre A.S.F. Teixeira, Vera Hagey, Daniel W. Tomaz, Diogo M. Muhr, Jonas Broccoli, Vania Castro, Diogo S. |
author_role |
author |
author2 |
Sessa, Alessandro Laranjeira, Cátia Raposo, Alexandre A.S.F. Teixeira, Vera Hagey, Daniel W. Tomaz, Diogo M. Muhr, Jonas Broccoli, Vania Castro, Diogo S. |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
ARCA |
dc.contributor.author.fl_str_mv |
Vasconcelos, Francisca F. Sessa, Alessandro Laranjeira, Cátia Raposo, Alexandre A.S.F. Teixeira, Vera Hagey, Daniel W. Tomaz, Diogo M. Muhr, Jonas Broccoli, Vania Castro, Diogo S. |
dc.subject.por.fl_str_mv |
Ascl1 Hes1 MyT1 Notch signaling Rbpj neurogenesis transcription |
topic |
Ascl1 Hes1 MyT1 Notch signaling Rbpj neurogenesis transcription |
description |
The generation of neurons from neural stem cells requires large-scale changes in gene expression that are controlled to a large extent by proneural transcription factors, such as Ascl1. While recent studies have characterized the differentiation genes activated by proneural factors, less is known on the mechanisms that suppress progenitor cell identity. Here, we show that Ascl1 induces the transcription factor MyT1 while promoting neuronal differentiation. We combined functional studies of MyT1 during neurogenesis with the characterization of its transcriptional program. MyT1 binding is associated with repression of gene transcription in neural progenitor cells. It promotes neuronal differentiation by counteracting the inhibitory activity of Notch signaling at multiple levels, targeting the Notch1 receptor and many of its downstream targets. These include regulators of the neural progenitor program, such as Hes1, Sox2, Id3, and Olig1. Thus, Ascl1 suppresses Notch signaling cell-autonomously via MyT1, coupling neuronal differentiation with repression of the progenitor fate. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-10-13T14:23:57Z 2016-10-04 2016-10-04T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.7/700 |
url |
http://hdl.handle.net/10400.7/700 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Francisca F. Vasconcelos, Alessandro Sessa, Cátia Laranjeira, Alexandre A.S.F. Raposo, Vera Teixeira, Daniel W. Hagey, Diogo M. Tomaz, Jonas Muhr, Vania Broccoli, Diogo S. Castro, MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate Neurogenesis, Cell Reports, Volume 17, Issue 2, 4 October 2016, Pages 469-483, ISSN 2211-1247, http://dx.doi.org/10.1016/j.celrep.2016.09.024. 10.1016/j.celrep.2016.09.024 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799130574709850112 |