title: Bone morphogenetic protein-2 acts upstream of myocyte-specific enhancer factor 2a to control embryonic cardiac contractility.
abstract: OBJECTIVE
  Cardiac contractility is regulated tightly as an extrinsic and intrinsic homeostatic mechanism to the heart. The molecular basis of the intrinsic system is largely unknown. Here, we test the hypothesis that bone morphogenetic protein-2 (BMP-2) mediates embryonic cardiac contractility upstream of myocyte-specific enhancer factor 2A (MEF2A).
  
  
  METHODS
  The BMP-2 and MEF2A expression pattern was analyzed by RT-PCR, Western blotting, whole-mount in situ hybridization, and an in vivo transgenic approach. The cardiac phenotype of BMP-2 and MEF2A knock-down zebrafish embryos was analysed. Cardiac contractions were recorded with a video camera. Myofibrillar organization was observed with transmission electron microscopy. Gene expression profiles were performed by quantitative real-time PCR analysis.
  
  
  RESULTS
  We demonstrate that BMP-2 and MEF2A are co-expressed in embryonic and neonatal cardiac myocytes. Furthermore, we provide evidence that BMP-2 is required for cardiac contractility in vitro and in vivo and that MEF2A expression can be activated by BMP-2 signaling in neonatal cardiomyocytes. BMP-2 is involved in the assembly of the cardiac contractile apparatus. Finally, we find that exogenous MEF2A is sufficient to rescue ventricular contractility defects in the absence of BMP-2 function.
  
  
  CONCLUSIONS
  In all, these observations indicate that BMP-2 and MEF2A are key components of a pathway that controls the cardiac ventricular contractility and suggest that the BMP2-MEF2A pathway can offer new opportunities for the treatment of heart failure.
authors: Department of Molecular Genetics, Shanghai Medical School and Key Laboratory of Molecular Medicine, Ministry of Education, Fudan University, 138 Yi Xueyuan Road, and Children's Hospital, Shanghai, 200032, P.R. China.
authors: Yue-Xiang
authors: YX
authors: Wang
authors: Lin-Xi
authors: LX
authors: Qian
authors: Dong
authors: D
authors: Liu
authors: Ling-Ling
authors: LL
authors: Yao
authors: Qiu
authors: Q
authors: Jiang
authors: Zhang
authors: Z
authors: Yu
authors: Yong-Hao
authors: YH
authors: Gui
authors: Tao P
authors: TP
authors: Zhong
authors: Hou-Yan
authors: HY
authors: Song
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000494:pharmacology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D005818:Genetic Engineering; D006321:Heart / Q000196:embryology; D006801:Humans; D026161:MADS Domain Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D064326:MEF2 Transcription Factors; D008969:Molecular Sequence Data; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000502:physiology*; D018006:Myogenic Regulatory Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D030781:Organisms, Genetically Modified; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics; D000099176:Noggin Protein
chemical_list: D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins; D000099176:Noggin Protein; C525718:BMP2 protein, human; C525720:Bmp2 protein, rat; C578035:MEF2A protein, human; C405936:bmp2b protein, zebrafish