Format

Send to

Choose Destination
J Clin Invest. 2006 Apr;116(4):929-39. Epub 2006 Mar 23.

GATA-6 regulates semaphorin 3C and is required in cardiac neural crest for cardiovascular morphogenesis.

Author information

1
Molecular Cardiology Research Center and the Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Abstract

GATA transcription factors play critical roles in restricting cell lineage differentiation during development. Here, we show that conditional inactivation of GATA-6 in VSMCs results in perinatal mortality from a spectrum of cardiovascular defects, including interrupted aortic arch and persistent truncus arteriosus. Inactivation of GATA-6 in neural crest recapitulates these abnormalities, demonstrating a cell-autonomous requirement for GATA-6 in neural crest-derived SMCs. Surprisingly, the observed defects do not result from impaired SMC differentiation but rather are associated with severely attenuated expression of semaphorin 3C, a signaling molecule critical for both neuronal and vascular patterning. Thus, the primary function of GATA-6 during cardiovascular development is to regulate morphogenetic patterning of the cardiac outflow tract and aortic arch. These findings provide new insights into the conserved functions of the GATA-4, -5, and -6 subfamily members and identify GATA-6 and GATA-6-regulated genes as candidates involved in the pathogenesis of congenital heart disease.

PMID:
16557299
PMCID:
PMC1409743
DOI:
10.1172/JCI27363
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for American Society for Clinical Investigation Icon for PubMed Central
Loading ...
Support Center