Hartman Institute for Therapeutic Organ Regeneration

Retinoid signaling required for normal heart development regulates GATA-4 in a pathway distinct from cardiomyocyte differentiation.

TitleRetinoid signaling required for normal heart development regulates GATA-4 in a pathway distinct from cardiomyocyte differentiation.
Publication TypeJournal Article
Year of Publication1999
AuthorsKostetskii I, Jiang Y, Kostetskaia E, Yuan S, Evans T, Zile M
JournalDev Biol
Volume206
Issue2
Pagination206-18
Date Published1999 Feb 15
ISSN0012-1606
KeywordsAnimals, Cell Differentiation, Coturnix, DNA-Binding Proteins, GATA4 Transcription Factor, Gene Expression Regulation, Developmental, Heart, Homeobox Protein Nkx-2.5, Homeodomain Proteins, In Situ Hybridization, Myocardium, Phenotype, Retinoids, Signal Transduction, Transcription Factors, Vitamin A, Vitamin A Deficiency, Xenopus Proteins
Abstract

Vitamin A is essential for normal embryonic cardiogenesis. The vitamin A-deficient phenotype in the avian embryo includes an abnormal heart tube closed at the sinus venosus and the absence of large vessels that normally connect the embryonic heart to the developing circulatory system. In vitamin A-deficient embryos the expression of cardiomyocyte differentiation genes, including atrial-specific myosin heavy chain, ventricular-specific myosin, and sarcomeric myosins as well as the putative cardiomyocyte specification gene Nkx-2.5, is not altered. However, the expression of transcription factor GATA-4 is severely decreased in the heart-forming regions of vitamin A-deficient stage 7-10 embryos. Significantly, GATA-4 transcripts are completely lacking in the lateral mesoderm posterior to the heart, in the area of the developing cardiac inflow tract that later displays prominent morphological defects, including a closed nonseptated heart lacking a sinus venosus. The administration of retinol to the vitamin A-deficient embryo restores GATA-4 expression and completely rescues the vitamin A-deficient phenotype. Our results indicate that GATA-4 is a component of the retinoid-mediated cardiogenic pathway unlinked to cardiomyocyte differentiation, but involved in the morphogenesis of the posterior heart tube and the development of the cardiac inflow tract.

DOI10.1006/dbio.1998.9139
Alternate JournalDev Biol
PubMed ID9986733

Weill Cornell Medicine
Hartman Institute for Therapeutic Organ Regeneration
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