dc.creator | Barnes, Ralston M. | es |
dc.creator | Harris, Ian S. | es |
dc.creator | Jaehnig, E. | es |
dc.creator | Sauls, Kimberly | es |
dc.creator | Sinha, Tanvi | es |
dc.creator | Rojas González, Anabel | es |
dc.creator | Schachterle, William | es |
dc.creator | McCulley, David J. | es |
dc.creator | Norris, Russell A. | es |
dc.creator | Black, Brian L. | es |
dc.date.accessioned | 2019-01-21T10:14:34Z | |
dc.date.available | 2019-01-21T10:14:34Z | |
dc.date.issued | 2016 | |
dc.identifier.citation | Barnes, R.M., Harris, I.S., Jaehnig, E.J., Sauls, K., Sinha, T., Rojas González, A.,...,Black, B.L. (2016). MEF2C regulates outflow tract alignment and transcriptional control of Tdgf1. Development, 143, 774-779. | |
dc.identifier.issn | 0950-1991 (impreso) | es |
dc.identifier.issn | 1477-9129 (electrónico) | es |
dc.identifier.uri | https://hdl.handle.net/11441/81762 | |
dc.description.abstract | Congenital heart defects are the most common birth defects in
humans, and those that affect the proper alignment of the outflow
tracts and septation of the ventricles are a highly significant cause of
morbidity and mortality in infants. A late differentiating population of
cardiac progenitors, referred to as the anterior second heart field
(AHF), gives rise to the outflow tract and the majority of the right
ventricle and provides an embryological context for understanding
cardiac outflow tract alignment and membranous ventricular septal
defects. However, the transcriptional pathways controlling AHF
development and their roles in congenital heart defects remain
incompletely elucidated. Here, we inactivated the gene encoding the
transcription factor MEF2C in the AHF in mice. Loss of Mef2c function
in the AHF results in a spectrum of outflow tract alignment defects
ranging from overriding aorta to double-outlet right ventricle and
dextro-transposition of the great arteries. We identify Tdgf1, which
encodes a Nodal co-receptor (also known as Cripto), as a direct
transcriptional target of MEF2C in the outflow tract via an AHFrestricted
Tdgf1 enhancer. Importantly, both the MEF2C and TDGF1
genes are associated with congenital heart defects in humans. Thus,
these studies establish a direct transcriptional pathway between the
core cardiac transcription factor MEF2C and the human congenital
heart disease gene TDGF1. Moreover, we found a range of outflow
tract alignment defects resulting from a single genetic lesion,
supporting the idea that AHF-derived outflow tract alignment
defects may constitute an embryological spectrum rather than
distinct anomalies. | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | Company of Biologists | es |
dc.relation.ispartof | Development, 143, 774-779. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | MEF2 | es |
dc.subject | Tdgf1 | es |
dc.subject | Cripto | es |
dc.subject | Enhancer | es |
dc.subject | Heart development | es |
dc.subject | Mouse | es |
dc.title | MEF2C regulates outflow tract alignment and transcriptional control of Tdgf1 | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.relation.publisherversion | https://doi.org/10.1242/dev.126383 | es |
dc.identifier.doi | 10.1242/dev.126383 | es |
idus.format.extent | 6 p. | es |
dc.journaltitle | Development | es |
dc.publication.volumen | 143 | es |
dc.publication.initialPage | 774 | es |
dc.publication.endPage | 779 | es |