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GATA-6 regulates semaphorin 3C and is required in cardiac neural crest for cardiovascular morphogenesis
John J. Lepore, … , Edward E. Morrisey, Michael S. Parmacek
John J. Lepore, … , Edward E. Morrisey, Michael S. Parmacek
Published April 3, 2006
Citation Information: J Clin Invest. 2006;116(4):929-939. https://doi.org/10.1172/JCI27363.
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Research Article Cardiology

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

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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.

Authors

John J. Lepore, Patricia A. Mericko, Lan Cheng, Min Min Lu, Edward E. Morrisey, Michael S. Parmacek

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Genotype distribution of embryonic and perinatal mortality 
following SM...

Genotype distribution of embryonic and perinatal mortality following SM22Cre- and Wnt1Cre-mediated conditional deletion of GATA-6


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