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Joint interpretation of AER/FGF and ZPA/SHH over time and space underlies hairy2 expression in the chick limb

2012-11Journal article Open access
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dc.contributor.authorSheeba, Caroline J.
dc.contributor.authorAndrade, Raquel P.
dc.contributor.authorPalmeirim, Isabel
dc.date.accessioned2018-12-07T14:57:58Z
dc.date.available2018-12-07T14:57:58Z
dc.date.issued2012-11
dc.description.abstractEmbryo development requires precise orchestration of cell proliferation and differentiation in both time and space. A molecular clock operating through gene expression oscillations was first described in the presomitic mesoderm (PSM) underlying periodic somite formation. Cycles of HES gene expression have been further identified in other progenitor cells, including the chick distal limb mesenchyme, embryonic neural progenitors and both mesenchymal and embryonic stem cells. In the limb, hairy2 is expressed in the distal mesenchyme, adjacent to the FGF source (AER) and along the ZPA-derived SHH gradient, the two major regulators of limb development. Here we report that hairy2 expression depends on joint AER/FGF and ZPA/SHH signaling. FGF plays an instructive role on hairy2, mediated by Erk and Akt pathway activation, while SHH acts by creating a permissive state defined by Gli3-A/Gli3-R>1. Moreover, we show that AER/FGF and ZPA/SHH present distinct temporal and spatial signaling properties in the distal limb mesenchyme: SHH acts at a long-term, long-range on hairy2, while FGF has a shortterm, short-range action. Our work establishes limb hairy2 expression as an output of integrated FGF and SHH signaling in time and space, providing novel clues for understanding the regulatory mechanisms underlying HES oscillations in multiple systems, including embryonic stem cell pluripotency. (C) 2012. Published by The Company of Biologists Ltd.
dc.description.sponsorshipFCT, Portugal [SFRH/BD/33176/2007]; Ciencia2007 Program Contract (Portuguese Government); IBB/CBME, LA; FCT, Portugal (National and FEDER COMPETE Program funds) [PTDC/SAU-OBD/099758/2008, PTDC/SAU-OBD/105111/2008]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1242/bio.20122386
dc.identifier.issn2046-6390
dc.identifier.urihttp://hdl.handle.net/10400.1/11789
dc.language.isoeng
dc.peerreviewedyes
dc.publisherCompany Of Biologists Ltd
dc.relationESTUDO DE INTERACÇÕES ENTRE O RELÓGIO MOLECULAR E A WAVEFRONT ASSOCIADOS À SEGMENTAÇÃO DE EMBRIÕES DE VERTEBRADOS
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.titleJoint interpretation of AER/FGF and ZPA/SHH over time and space underlies hairy2 expression in the chick limb
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleESTUDO DE INTERACÇÕES ENTRE O RELÓGIO MOLECULAR E A WAVEFRONT ASSOCIADOS À SEGMENTAÇÃO DE EMBRIÕES DE VERTEBRADOS
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%2FBD%2F33176%2F2007/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.endPage1110
oaire.citation.issue11
oaire.citation.startPage1102
oaire.citation.titleBiology Open
oaire.citation.volume1
oaire.fundingStream3599-PPCDT
oaire.fundingStream5876-PPCDTI
person.familyNameSheeba
person.familyNameAndrade
person.familyNamePalmeirim
person.givenNameCaroline Jeya
person.givenNameRaquel
person.givenNameIsabel
person.identifier437977
person.identifier.ciencia-id2312-360B-227A
person.identifier.ciencia-id141A-4DE2-6FF3
person.identifier.orcid0000-0001-5357-4743
person.identifier.orcid0000-0002-0397-5917
person.identifier.orcid0000-0003-2282-7829
person.identifier.ridB-5177-2011
person.identifier.scopus-author-id6504257550
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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