Defects in cardiomyocyte differentiation and cardiac morphogenesis cause heart malformations affecting almost one in every 100 children, but the mechanisms that regulate such events remain largely unknown. In the April 1 online edition of Nature Genetics, Paul Gottlieb and colleagues from University of Texas at Austin, US, show that Bop encodes a muscle-restricted protein that is essential for cardiac differentiation and morphogenesis (Nat Genet 2002, DOI: 10.1038/ng866).
Gottlieb et al. used a modified subtractive hybridization approach and identified early cardiac-specific genes in chick and murine embryos. They observed that Bop was expressed specifically in cardiac and skeletal muscle precursors and in cardiomyocytes throughout organ development, beginning before cardiac differentiation. The protein m-Bop can interact with histone deacetylases and can function as a transcriptional repressor.
They also showed that targeted deletion of Bop in mice disrupted maturation of ventricular cardiomyocytes and interfered with formation of the right ventricle. In addition, normal expression in cardiomyocyte precursors of Hand2, a transcription factor essential for right ventricular development, was dependent upon m-Bop.
"Now with several genes - including Bop and Hand2 - identified as controllers of heart development, preventives [of pediatric heart problems] are finally conceivable," said Deepak Srivastava, the senior author of the paper. "The next major research steps to achieve this goal are already under way: to catalog and understand the mechanisms of all genes with critical roles in heart development and to correlate specific gene mutations with each specific heart defect in children."
Gottlieb PD, Pierce SA, Sims III RJ, Yamagishi H, Weihe EK, Harriss JV, Maika SD, Kuziel WA, King HL, Olson EN et al.: Bop encodes a muscle-restricted protein containing MYND and SET domains and is essential for cardiac differentiation and morphogenesis. Nat Genet 2002, DOI: 10.1038/ng866.
University of Texas at Austin