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First published online 2 December 2004
doi: 10.1242/dev.01562
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1 Department of Molecular Biology, University of Texas Southwestern Medical
Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9148, USA
2 Department of Pathology, University of Texas Southwestern Medical Center, 6000
Harry Hines Boulevard, Dallas, TX 75390-9148, USA
3 Center for Cardiovascular Development, Department of Medicine, Molecular and
Cellular Biology, and Molecular Physiology and Biophysics, Baylor College of
Medicine, Houston, TX 77030-3498, USA
4 Department of Pediatrics, University of Texas Southwestern Medical Center,
6000 Harry Hines Boulevard, Dallas, TX 75390-9148, USA
Author for correspondence (e-mail:
eric.olson{at}utsouthwestern.edu)
Accepted 1 November 2004
The basic helix-loop-helix transcription factors Hand1 and Hand2 display dynamic and spatially restricted expression patterns in the developing heart. Mice that lack Hand2 die at embryonic day 10.5 from right ventricular hypoplasia and vascular defects, whereas mice that lack Hand1 die at embryonic day 8.5 from placental and extra-embryonic abnormalities that preclude analysis of its potential role in later stages of heart development. To determine the cardiac functions of Hand1, we generated mice harboring a conditional Hand1-null allele and excised the gene by cardiac-specific expression of Cre recombinase. Embryos homozygous for the cardiac Hand1 gene deletion displayed defects in the left ventricle and endocardial cushions, and exhibited dysregulated ventricular gene expression. However, these embryos survived until the perinatal period when they died from a spectrum of cardiac abnormalities. Creation of Hand1/2 double mutant mice revealed gene dose-sensitive functions of Hand transcription factors in the control of cardiac morphogenesis and ventricular gene expression. These findings demonstrate that Hand factors play pivotal and partially redundant roles in cardiac morphogenesis, cardiomyocyte differentiation and cardiac-specific transcription.
Key words: Mouse, Hand1, Hand2, Cardiac ventricles
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