Cerberus is a feedback inhibitor of Nodal asymmetric signaling in the chick embryo

Detalhes bibliográficos
Autor(a) principal: Tavares, Ana Teresa
Data de Publicação: 2007
Outros Autores: Andrade, Sofia, Silva, Ana Cristina, Belo, José A.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.1/11578
Resumo: The TGF-beta-related molecule Nodal plays an essential and conserved role in left-right patterning of the vertebrate embryo. Previous reports have shown that the zebrafish and mouse Cerberus-related proteins Charon and Cerberus-like-2 (Cerl-2), respectively, act in the node region to prevent the Nodal signal from crossing to the right side, whereas chick Cerberus (cCer) has an unclear function in the left-side mesoderm. In this study, we investigate the transcriptional regulation and function of cCer in left-right development. By analyzing the enhancer activity of cCer 5' genomic sequences in electroporated chick embryos, we identified a cCer left-side enhancer that contains two FoxH1 and one SMAD binding site. We show that these Nodal-responsive elements are necessary and sufficient for the activation of transcription in the left-side mesoderm. In transgenic mouse embryos, cCer regulatory sequences behave as in chick embryos, suggesting that the cis-regulatory sequences of Cerberus-related genes have diverged during vertebrate evolution. Moreover, our findings from cCer overexpression and knockdown experiments indicate that cCer is a negative-feedback regulator of Nodal asymmetric signaling. We propose that cCer and mouse Cerl-2 have evolved distinct regulatory mechanisms but retained a conserved function in left-right development, which is to restrict Nodal activity to the left side of the embryo.
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spelling Cerberus is a feedback inhibitor of Nodal asymmetric signaling in the chick embryoEarly mouse embryoVertebrate developmentPrimitive streakGene-expressionSecreted factorAxis formationLateral plateTgf-BetaBmpAntagonistThe TGF-beta-related molecule Nodal plays an essential and conserved role in left-right patterning of the vertebrate embryo. Previous reports have shown that the zebrafish and mouse Cerberus-related proteins Charon and Cerberus-like-2 (Cerl-2), respectively, act in the node region to prevent the Nodal signal from crossing to the right side, whereas chick Cerberus (cCer) has an unclear function in the left-side mesoderm. In this study, we investigate the transcriptional regulation and function of cCer in left-right development. By analyzing the enhancer activity of cCer 5' genomic sequences in electroporated chick embryos, we identified a cCer left-side enhancer that contains two FoxH1 and one SMAD binding site. We show that these Nodal-responsive elements are necessary and sufficient for the activation of transcription in the left-side mesoderm. In transgenic mouse embryos, cCer regulatory sequences behave as in chick embryos, suggesting that the cis-regulatory sequences of Cerberus-related genes have diverged during vertebrate evolution. Moreover, our findings from cCer overexpression and knockdown experiments indicate that cCer is a negative-feedback regulator of Nodal asymmetric signaling. We propose that cCer and mouse Cerl-2 have evolved distinct regulatory mechanisms but retained a conserved function in left-right development, which is to restrict Nodal activity to the left side of the embryo.Company Of Biologists LtdSapientiaTavares, Ana TeresaAndrade, SofiaSilva, Ana CristinaBelo, José A.2018-12-07T14:53:34Z2007-062007-06-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.1/11578eng0950-199110.1242/dev.000901info: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:RCAAP2023-07-24T10:23:25Zoai:sapientia.ualg.pt:10400.1/11578Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:03:03.903199Repositório 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 Cerberus is a feedback inhibitor of Nodal asymmetric signaling in the chick embryo
title Cerberus is a feedback inhibitor of Nodal asymmetric signaling in the chick embryo
spellingShingle Cerberus is a feedback inhibitor of Nodal asymmetric signaling in the chick embryo
Tavares, Ana Teresa
Early mouse embryo
Vertebrate development
Primitive streak
Gene-expression
Secreted factor
Axis formation
Lateral plate
Tgf-Beta
Bmp
Antagonist
title_short Cerberus is a feedback inhibitor of Nodal asymmetric signaling in the chick embryo
title_full Cerberus is a feedback inhibitor of Nodal asymmetric signaling in the chick embryo
title_fullStr Cerberus is a feedback inhibitor of Nodal asymmetric signaling in the chick embryo
title_full_unstemmed Cerberus is a feedback inhibitor of Nodal asymmetric signaling in the chick embryo
title_sort Cerberus is a feedback inhibitor of Nodal asymmetric signaling in the chick embryo
author Tavares, Ana Teresa
author_facet Tavares, Ana Teresa
Andrade, Sofia
Silva, Ana Cristina
Belo, José A.
author_role author
author2 Andrade, Sofia
Silva, Ana Cristina
Belo, José A.
author2_role author
author
author
dc.contributor.none.fl_str_mv Sapientia
dc.contributor.author.fl_str_mv Tavares, Ana Teresa
Andrade, Sofia
Silva, Ana Cristina
Belo, José A.
dc.subject.por.fl_str_mv Early mouse embryo
Vertebrate development
Primitive streak
Gene-expression
Secreted factor
Axis formation
Lateral plate
Tgf-Beta
Bmp
Antagonist
topic Early mouse embryo
Vertebrate development
Primitive streak
Gene-expression
Secreted factor
Axis formation
Lateral plate
Tgf-Beta
Bmp
Antagonist
description The TGF-beta-related molecule Nodal plays an essential and conserved role in left-right patterning of the vertebrate embryo. Previous reports have shown that the zebrafish and mouse Cerberus-related proteins Charon and Cerberus-like-2 (Cerl-2), respectively, act in the node region to prevent the Nodal signal from crossing to the right side, whereas chick Cerberus (cCer) has an unclear function in the left-side mesoderm. In this study, we investigate the transcriptional regulation and function of cCer in left-right development. By analyzing the enhancer activity of cCer 5' genomic sequences in electroporated chick embryos, we identified a cCer left-side enhancer that contains two FoxH1 and one SMAD binding site. We show that these Nodal-responsive elements are necessary and sufficient for the activation of transcription in the left-side mesoderm. In transgenic mouse embryos, cCer regulatory sequences behave as in chick embryos, suggesting that the cis-regulatory sequences of Cerberus-related genes have diverged during vertebrate evolution. Moreover, our findings from cCer overexpression and knockdown experiments indicate that cCer is a negative-feedback regulator of Nodal asymmetric signaling. We propose that cCer and mouse Cerl-2 have evolved distinct regulatory mechanisms but retained a conserved function in left-right development, which is to restrict Nodal activity to the left side of the embryo.
publishDate 2007
dc.date.none.fl_str_mv 2007-06
2007-06-01T00:00:00Z
2018-12-07T14:53:34Z
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/10400.1/11578
url http://hdl.handle.net/10400.1/11578
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0950-1991
10.1242/dev.000901
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 Company Of Biologists Ltd
publisher.none.fl_str_mv Company Of Biologists Ltd
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
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instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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collection 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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