dc.contributor.author | Captur, Gabriella | |
dc.contributor.author | Wilson, Robert | |
dc.contributor.author | Bennett, Michael F. | |
dc.contributor.author | Luxan, Guillermo | |
dc.contributor.author | Nasis, Arthur | |
dc.contributor.author | de la Pompa, Jose Luis | |
dc.contributor.author | Moon, James C. | |
dc.contributor.author | Mohun, Timothy J. | |
dc.date.accessioned | 2017-10-30T13:15:40Z | |
dc.date.available | 2017-10-30T13:15:40Z | |
dc.date.issued | 2016 | |
dc.identifier | ISI:000383723600012 | |
dc.identifier.citation | J Anat. 2016; 229(2):314-25 | |
dc.identifier.issn | 0021-8782 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/5206 | |
dc.description.abstract | Formation of trabeculae in the embryonic heart and the remodelling that occurs prior to birth is a conspicuous, but poorly understood, feature of vertebrate cardiogenesis. Mutations disrupting trabecular development in the mouse are frequently embryonic lethal, testifying to the importance of the trabeculae, and aberrant trabecular structure is associated with several human cardiac pathologies. Here, trabecular architecture in the developing mouse embryo has been analysed using high-resolution episcopic microscopy (HREM) and three-dimensional (3D) modelling. This study shows that at all stages from mid-gestation to birth, the ventricular trabeculae comprise a complex meshwork of myocardial strands. Such an arrangement defies conventional methods of measurement, and an approach based upon fractal algorithms has been used to provide an objective measure of trabecular complexity. The extent of trabeculation as it changes along the length of left and right ventricles has been quantified, and the changes that occur from formation of the four-chambered heart until shortly before birth have been mapped. This approach not only measures qualitative features evident from visual inspection of 3D models, but also detects subtle, consistent and regionally localised differences that distinguish each ventricle and its developmental stage. Finally, the combination of HREM imaging and fractal analysis has been applied to analyse changes in embryonic heart structure in a genetic mouse model in which trabeculation is deranged. It is shown that myocardial deletion of the Notch pathway component Mib1 (Mib1(flox/flox); cTnT-cre) results in a complex array of abnormalities affecting trabeculae and other parts of the heart. | |
dc.description.sponsorship | This work was supported by funding to TJM from the Medical Research Council (U117562103); to JCM by the Higher Education Funding Council for England; to JLdlP and GL by grants SAF2010-17555 and SAF2013-45543-R from the Spanish Ministry of Economy and Competitiveness (MINECO); and to GC by a research fellowship at the University College London Biomedical Research Centre from the UK National Institutes of Health Research Cardiometabolic Programme. | |
dc.language.iso | eng | |
dc.publisher | Wiley | |
dc.type.hasVersion | VoR | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Cardiac embryology | |
dc.subject | Cardiogenesis | |
dc.subject | Developmental biology | |
dc.subject | Non-compaction cardiomyopathy | |
dc.subject | VENTRICULAR NONCOMPACTION CARDIOMYOPATHY | |
dc.subject | RESOLUTION EPISCOPIC MICROSCOPY | |
dc.subject | CONDUCTION SYSTEM | |
dc.subject | HEART DEVELOPMENT | |
dc.subject | NON-COMPACTION | |
dc.subject | PROLIFERATION | |
dc.subject | ARCHITECTURE | |
dc.subject | EXPRESSION | |
dc.subject | MUTATIONS | |
dc.title | Morphogenesis of myocardial trabeculae in the mouse embryo | |
dc.type | journal article | |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 27020702 | |
dc.format.volume | 229 | |
dc.format.page | 314-325 | |
dc.identifier.doi | 10.1111/joa.12465 | |
dc.contributor.funder | Medical Research Council (Reino Unido) | |
dc.contributor.funder | Higher Education Funding Council for England | |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | National Institute for Health Research (Reino Unido) | |
dc.description.peerreviewed | Sí | |
dc.identifier.e-issn | 1469-7580 | |
dc.relation.publisherversion | https://doi.org/10.1111/joa.12465 | |
dc.identifier.journal | Journal of Anatomy | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Señalización Intercelular durante el Desarrollo y la Enfermedad Cardiovascular | |
dc.repisalud.institucion | CNIC | |
dc.relation.projectID | MINECO/ICTI2013-2016/SAF2013-45543-R | es_ES |
dc.rights.accessRights | open access | es_ES |