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

dc.contributor.authorTavares, Ana Teresa
dc.contributor.authorAndrade, Sofia
dc.contributor.authorSilva, Ana Cristina
dc.contributor.authorBelo, José A.
dc.date.accessioned2018-12-07T14:53:34Z
dc.date.available2018-12-07T14:53:34Z
dc.date.issued2007-06
dc.description.abstractThe 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.
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1242/dev.000901
dc.identifier.issn0950-1991
dc.identifier.urihttp://hdl.handle.net/10400.1/11578
dc.language.isoeng
dc.peerreviewedyes
dc.publisherCompany Of Biologists Ltd
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectEarly mouse embryo
dc.subjectVertebrate development
dc.subjectPrimitive streak
dc.subjectGene-expression
dc.subjectSecreted factor
dc.subjectAxis formation
dc.subjectLateral plate
dc.subjectTgf-Beta
dc.subjectBmp
dc.subjectAntagonist
dc.titleCerberus is a feedback inhibitor of Nodal asymmetric signaling in the chick embryo
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage2060
oaire.citation.issue11
oaire.citation.startPage2051
oaire.citation.titleDevelopment
oaire.citation.volume134
person.familyNameBelo
person.givenNameJosé A.
person.identifier.ciencia-idBF13-08E9-25E6
person.identifier.orcid0000-0001-7384-0949
person.identifier.ridF-4444-2012
person.identifier.scopus-author-id6602141392
rcaap.rightsopenAccess
rcaap.typearticle
relation.isAuthorOfPublication4bebeb48-6fac-41a9-8363-f849def5e019
relation.isAuthorOfPublication.latestForDiscovery4bebeb48-6fac-41a9-8363-f849def5e019

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