Bmp Signaling Regulates Myocardial Differentiation from Cardiac Progenitors Through a MicroRNA-Mediated Mechanism Academic Article uri icon

abstract

  • MicroRNAs (miRNAs) are small, noncoding RNAs thatregulate gene expression posttranscriptionally. We investigated the hypothesis that bone morphogenetic protein (Bmp) signaling regulates miRNAs in cardiac progenitor cells. Bmp2 and Bmp4 regulate OFT myocardial differentiation via regulation of themiRNA-17-92 cluster. In Bmp mutant embryos, myocardial differentiation was delayed, and multiple miRNAs encoded by miRNA-17-92 were reduced. We uncovered functional miRNA-17-92 seed sequences within the 3' UTR of cardiac progenitor genes such as Isl1 and Tbx1. In both Bmp and miRNA-17-92 mutant embryos, Isl1 and Tbx1 expression failed to be correctly downregulated. Transfection experiments indicated that miRNA-17 and miRNA-20a directly repressed Isl1 and Tbx1. Genetic interaction studies uncovered a synergistic interaction between miRNA-17-92 cluster and Bmp4, providing direct invivo evidence for the Bmp-miRNA-17-92 regulatory pathway. Our findings indicate that Bmp signaling directly regulates a miRNA-mediated effector mechanism that downregulates cardiac progenitor genes and enhances myocardial differentiation.

published proceedings

  • Dev Cell

altmetric score

  • 3

author list (cited authors)

  • Wang, J., Greene, S. B., Bonilla-Claudio, M., Tao, Y. e., Zhang, J., Bai, Y., ... Martin, J. F.

citation count

  • 146

complete list of authors

  • Wang, Jun||Greene, Stephanie B||Bonilla-Claudio, Margarita||Tao, Ye||Zhang, Jue||Bai, Yan||Huang, Zheng||Black, Brian L||Wang, Fen||Martin, James F

publication date

  • January 2010