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Sonic hedgehog in temporal control of somite formation

dc.contributor.authorResende, Tatiana P.
dc.contributor.authorFerreira, Monica
dc.contributor.authorTeillet, Marie-Aimee
dc.contributor.authorTavares, Ana Teresa
dc.contributor.authorAndrade, Raquel P.
dc.contributor.authorPalmeirim, Isabel
dc.date.accessioned2018-12-07T14:57:59Z
dc.date.available2018-12-07T14:57:59Z
dc.date.issued2014-11
dc.description.abstractVertebrate embryo somite formation is temporally controlled by the cyclic expression of somitogenesis clock genes in the presomitic mesoderm (PSM). The somitogenesis clock is believed to be an intrinsic property of this tissue, operating independently of embryonic midline structures and the signaling molecules produced therein, namely Sonic hedgehog (Shh). This work revisits the notochord signaling contribution to temporal control of PSM segmentation by assessing the rate and number of somites formed and somitogenesis molecular clock gene expression oscillations upon notochord ablation. The absence of the notochord causes a delay in somite formation, accompanied by an increase in the period of molecular clock oscillations. Shh is the notochord-derived signal responsible for this effect, as these alterations are recapitulated by Shh signaling inhibitors and rescued by an external Shh supply. We have characterized chick smoothened expression pattern and have found that the PSM expresses both patched1 and smoothened Shh signal transducers. Upon notochord ablation, patched1, gli1, and fgf8 are down-regulated, whereas gli2 and gli3 are overexpressed. Strikingly, notochord-deprived PSM segmentation rate recovers over time, concomitant with raldh2 overexpression. Accordingly, exogenous RA supplement rescues notochord ablation effects on somite formation. A model is presented in which Shh and RA pathways converge to inhibit PSM Gli activity, ensuring timely somite formation. Altogether, our data provide evidence that a balance between different pathways ensures the robustness of timely somite formation and that notochord-derived Shh is a component of the molecular network regulating the pace of the somitogenesis clock.
dc.description.sponsorshipFundacao para a Ciencia e a Tecnologia (FCT), Portugal [SFRH/BD/27796/2006, PTDC/SAU-OBD/099758/2008, PTDC/SAU-OBD/105111/2008]; Portuguese Government; EU; IBB/CBME, LA
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1073/pnas.1000979107
dc.identifier.issn0027-8424
dc.identifier.urihttp://hdl.handle.net/10400.1/11803
dc.language.isoeng
dc.peerreviewedyes
dc.publisherNatl Acad Sciences
dc.relationMolecular parallelisms in vertebrate somitogenesis and limb development
dc.relationThe role of molecular clock genes in temporal control of mesoderm patterning in vertebrate embryos
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectPresomitic mesoderm
dc.subjectSegmentation clock
dc.subjectSignaling pathways
dc.subjectGene-expression
dc.subjectRetinoic acid
dc.subjectChick limb
dc.subjectSomitogenesis
dc.subjectHomolog
dc.subjectInduction
dc.subjectNotochord
dc.titleSonic hedgehog in temporal control of somite formation
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleMolecular parallelisms in vertebrate somitogenesis and limb development
oaire.awardTitleThe role of molecular clock genes in temporal control of mesoderm patterning in vertebrate embryos
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F27796%2F2006/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-OBD%2F099758%2F2008/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876-PPCDTI/PTDC%2FSAU-OBD%2F105111%2F2008/PT
oaire.citation.endPage12912
oaire.citation.issue29
oaire.citation.startPage121
oaire.citation.startPage12907
oaire.citation.titleProceedings of the National Academy of Sciences
oaire.citation.volume107
oaire.fundingStreamSFRH
oaire.fundingStream3599-PPCDT
oaire.fundingStream5876-PPCDTI
person.familyNameResende
person.familyNameAndrade
person.familyNamePalmeirim
person.givenNameTatiana
person.givenNameRaquel
person.givenNameIsabel
person.identifier.ciencia-id2312-360B-227A
person.identifier.ciencia-id141A-4DE2-6FF3
person.identifier.orcid0000-0002-1116-5770
person.identifier.orcid0000-0002-0397-5917
person.identifier.orcid0000-0003-2282-7829
person.identifier.ridB-4256-2011
person.identifier.scopus-author-id36612169900
person.identifier.scopus-author-id7103114918
person.identifier.scopus-author-id6603305227
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccess
rcaap.typearticle
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