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A tissue-specific, Gata6-driven transcriptional program instructs remodeling of the mature arterial tree

2017-09-27Journal article Open access
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dc.contributor.authorLosa, Marta
dc.contributor.authorLatorre, Victor
dc.contributor.authorAndrabi, Munazah
dc.contributor.authorLadam, Franck
dc.contributor.authorSagerström, Charles
dc.contributor.authorNovoa, Ana
dc.contributor.authorZarrineh, Peyman
dc.contributor.authorBridoux, Laure
dc.contributor.authorHanley, Neil A
dc.contributor.authorMallo, Moises
dc.contributor.authorBobola, Nicoletta
dc.date.accessioned2017-10-23T14:31:29Z
dc.date.available2017-10-23T14:31:29Z
dc.date.issued2017-09-27
dc.descriptionThis deposit is composed by the main article plus the supplementary materials of the publication.pt_PT
dc.description.abstractConnection of the heart to the systemic circulation is a critical developmental event that requires selective preservation of embryonic vessels (aortic arches). However, why some aortic arches regress while others are incorporated into the mature aortic tree remains unclear. By microdissection and deep sequencing in mouse, we find that neural crest (NC) only differentiates into vascular smooth muscle cells (SMCs) around those aortic arches destined for survival and reorganization, and identify the transcription factor Gata6 as a crucial regulator of this process. Gata6 is expressed in SMCs and its target genes activation control SMC differentiation. Furthermore, Gata6 is sufficient to promote SMCs differentiation in vivo, and drive preservation of aortic arches that ought to regress. These findings identify Gata6-directed differentiation of NC to SMCs as an essential mechanism that specifies the aortic tree, and provide a new framework for how mutations in GATA6 lead to congenital heart disorders in humans.pt_PT
dc.description.sponsorshipMedical Research Council grant: (MR/L009986/1); Biotechnology and Biological Sciences Research Council grant: (BB/N00907X/1); National Institute of Neurological Disorders and Stroke grant: (NS038183).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationeLife 2017;6:e31362 doi: 10.7554/eLife.31362pt_PT
dc.identifier.doi10.7554/eLife.31362pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/789
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publishereLife Sciences Publicationspt_PT
dc.relationMR/L009986/1pt_PT
dc.relationBB/N00907X/1pt_PT
dc.relationNS038183pt_PT
dc.relation.publisherversionhttps://elifesciences.org/articles/31362pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectdevelopmental biologypt_PT
dc.subjectembryopt_PT
dc.subjectgreat vesselspt_PT
dc.subjectmousept_PT
dc.subjectneural crestpt_PT
dc.subjectsmooth muscle cellspt_PT
dc.subjectstem cellspt_PT
dc.subjecttranscriptionpt_PT
dc.titleA tissue-specific, Gata6-driven transcriptional program instructs remodeling of the mature arterial treept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage22pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titleeLifept_PT
oaire.citation.volume6pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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