Previous Article |
Table of Contents
| Next Article 
BIOLOGICAL SCIENCES / DEVELOPMENTAL BIOLOGY
Vertebrate heart growth is regulated by functional antagonism between Gridlock and Gata5
*Departments of Medicine and Cell and Developmental Biology, and Department of Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232; and Gladstone Institute of Cardiovascular Disease, Department of Pediatrics, University of California, San Francisco, CA 94158
Edited by Eric N. Olson, University of Texas Southwestern Medical Center, Dallas, TX, and approved July 20, 2007 (received for review March 12, 2007)
Embryonic organs attain their final dimensions through the generation of proper cell number and size, but the control mechanisms remain obscure. Here, we establish Gridlock (Grl), a Hairy-related basic helix–loop–helix (bHLH) transcription factor, as a negative regulator of cardiomyocyte proliferative growth in zebrafish embryos. Mutations in grl cause an increase in expression of a group of immediate-early growth genes, myocardial genes, and development of hyperplastic hearts. Conversely, cardiomyocytes with augmented Grl activity have diminished cell volume and fail to divide, resulting in a marked reduction in heart size. Both bHLH domain and carboxyl region are required for Grl negative control of myocardial proliferative growth. These Grl-induced cardiac effects are counterbalanced by the transcriptional activator Gata5 but not Gata4, which promotes cardiomyocyte expansion in the embryo. Biochemical analyses show that Grl forms a complex with Gata5 through the carboxyl region and can repress Gata5-mediated transcription via the bHLH domain. Hence, our studies suggest that Grl regulates embryonic heart growth via opposing Gata5, at least in part through their protein interactions in modulating gene expression.
cardiomyocyte | proliferation | size control | transcription
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. DQ886664).
This article contains supporting information online at www.pnas.org/cgi/content/full/0702240104/DC1.
To whom correspondence should be addressed at: Vanderbilt University School of Medicine, 358 Preston Research Building, 2220 Pierce Avenue, Nashville, TN 37232. E-mail: tao.zhong{at}vanderbilt.edu
© 2007 by The National Academy of Sciences of the USA
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg What's this?
