Epigenetic control of cardiomyocyte production in response to a stress during the medaka heart development

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2010.01.014 Byline: Yusuke Taneda (a), Sayaka Konno (a), Shinji Makino (b), Mai Morioka (a), Keiichi Fukuda (b), Yoshiyuki Imai (a), Akira Kudo (a), Atsushi Kawakami (a) Keywords: Medaka; Mutant; Heart development; Myosin heavy chain; Transgenic; Epigenetic regulation Abstract: The size and morphology of organs are largely determined by a genetic program. However in some cases, an epigenetic mechanism influences the process of organ development. Particularly, epigenetic factors such as hemodynamic stress and blood pressure affect the morphogenesis of cardiac chambers and valves. Here, we report that the epigenetic influences affect the cardiomyocyte production. Taking advantage of longer developmental period of medaka fish, we could examine the later emerging tissue responses to the defect of ventricular beating, which occurred in the hozuki (hoz) mutant that harbors the mutated ventricular myosin heavy chain (vmhc) gene. The mutant showed a remarkable ventricular enlargement, and we showed that this enlargement was due to an excess production of ventricular cardiomyocytes in addition to the lack of concentric chamber growth. By experimental blockade of blood flow, we demonstrated that an elevated cardiac pressure was responsible for the aberrant cardiomyocyte production. From these data, we propose that the epigenetic tissue response to a stressed situation controls the production of cardiomyocytes to attain a fine tuning of heart formation. Author Affiliation: (a) Department of Biological Information, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan (b) Department of Regenerative Medicine and Advanced Cardiac Therapeutics, Keio University School of Medicine, Shinjuku, Tokyo, Japan Article History: Received 12 August 2009; Revised 12 January 2010; Accepted 12 January 2010