[HTML][HTML] GATA-6 regulates semaphorin 3C and is required in cardiac neural crest for cardiovascular morphogenesis
JJ Lepore, PA Mericko, L Cheng, MM Lu… - The Journal of …, 2006 - Am Soc Clin Investig
JJ Lepore, PA Mericko, L Cheng, MM Lu, EE Morrisey, MS Parmacek
The Journal of clinical investigation, 2006•Am Soc Clin InvestigGATA 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 …
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 …
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.
The Journal of Clinical Investigation