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Analysis of opo cis-regulatory landscape uncovers Vsx2 requirement in early eye morphogenesis

2015-05-12Journal article Open access
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dc.contributor.authorI, Gago-Rodrigues
dc.contributor.authorFernández-Miñán, Ana
dc.contributor.authorLetelier, Joaquin
dc.contributor.authorNaranjo, Silvia
dc.contributor.authorTena, Juan J.
dc.contributor.authorGómez-Skarmeta, José L.
dc.contributor.authorMartinez-Morales, Juan R.
dc.date.accessioned2017-01-20T14:04:30Z
dc.date.available2017-01-20T14:04:30Z
dc.date.issued2015-05-12
dc.description.abstractThe self-organized morphogenesis of the vertebrate optic cup entails coupling the activation of the retinal gene regulatory network to the constriction-driven infolding of the retinal epithelium. Yet the genetic mechanisms underlying this coordination remain largely unexplored. Through phylogenetic footprinting and transgenesis in zebrafish, here we examine the cis-regulatory landscape of opo, an endocytosis regulator essential for eye morphogenesis. Among the different conserved enhancers identified, we isolate a single retina-specific element (H6_10137) and show that its activity depends on binding sites for the retinal determinant Vsx2. Gain- and loss-of-function experiments and ChIP analyses reveal that Vsx2 regulates opo expression through direct binding to this retinal enhancer. Furthermore, we show that vsx2 knockdown impairs the primary optic cup folding. These data support a model by which vsx2, operating through the effector gene opo, acts as a central transcriptional node that coordinates neural retina patterning and optic cup invagination in zebrafish.pt_PT
dc.description.sponsorshipBFU2013-41322-P (Espanha); Proyecto de Excelencia BIO-396(Espanha); CSIC-010CR0002(Espanha); BFU2008-04362(Espanha); BFU2011-22916(Espanha); P11-CVI-7256(Espanha)
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1038/ncomms8054pt_PT
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/10400.1/8967
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherNature Publishing Grouppt_PT
dc.relationCHARACTERIZATION OF THE REGULATORY LOGIC GOVERNING THE OJOPLANO LOCUS: INVESTIGATING OPO LINK TO HUMAN HEREDITARY DISEASES
dc.subjectAnimalspt_PT
dc.subjectEnhancer Elementspt_PT
dc.subjectEpigenesispt_PT
dc.subjectEyept_PT
dc.subjectEye proteinspt_PT
dc.subjectGene expression regulationpt_PT
dc.subjectGene knockdown techniquespt_PT
dc.subjectGenomicspt_PT
dc.subjectHomeodomain proteinspt_PT
dc.subjectHumanspt_PT
dc.subjectPhylogenypt_PT
dc.subjectProtein bindingpt_PT
dc.subjectProtein footprintingpt_PT
dc.subjectRNA splicingpt_PT
dc.subjectRNApt_PT
dc.subjectRetinal neuronspt_PT
dc.subjectZebrafishpt_PT
dc.subjectZebrafish proteinspt_PT
dc.subjectGenetically modifiedpt_PT
dc.subjectGeneticpt_PT
dc.subjectMessengerpt_PT
dc.subjectDevelopmentalpt_PT
dc.titleAnalysis of opo cis-regulatory landscape uncovers Vsx2 requirement in early eye morphogenesispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCHARACTERIZATION OF THE REGULATORY LOGIC GOVERNING THE OJOPLANO LOCUS: INVESTIGATING OPO LINK TO HUMAN HEREDITARY DISEASES
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F60489%2F2009/PT
oaire.citation.conferencePlaceEUApt_PT
oaire.citation.startPage7054pt_PT
oaire.citation.titleNature Communicationspt_PT
oaire.citation.volume6pt_PT
person.familyNameGago Rodrigues
person.givenNameInês
person.identifier.ciencia-id5019-5D4A-15B8
person.identifier.orcid0000-0002-9745-0467
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication0e1f7ddd-5169-4522-a1cf-966e4e75a164
relation.isAuthorOfPublication.latestForDiscovery0e1f7ddd-5169-4522-a1cf-966e4e75a164
relation.isProjectOfPublicationc2bb8fb3-14b6-49fc-b69f-853ea81601a4
relation.isProjectOfPublication.latestForDiscoveryc2bb8fb3-14b6-49fc-b69f-853ea81601a4

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