Cerberus is a feedback inhibitor of Nodal asymmetric signaling in the chick embryo
Autor(a) principal: | |
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Data de Publicação: | 2007 |
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/10400.1/11578 |
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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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 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) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799133265209065472 |