title: An in vivo map of bone morphogenetic protein 2 post-transcriptional repression in the heart.
abstract: The Bmp2 3'untranslated region (UTR) sequence bears a sequence conserved between mammals and fishes that can post-transcriptionally activate or repress protein synthesis. We developed a map of embryonic cells in the mouse where this potent Bmp2 regulatory sequence functions by using a lacZ reporter transgene with a 3'UTR bearing two loxP sites flanking the ultra-conserved sequence. Cre-recombinase-mediated deletion of the ultra-conserved sequence caused strong ectopic expression in proepicardium, epicardium and epicardium-derived cells (EPDC) and in tissues with known epicardial contributions (coronary vessels and valves). Transient transfections of reporters in the epicardial/mesothelial cell (EMC) line confirmed this repression. Ectopic expression of the recombined transgene also occurred in the aorta, outlet septum, posterior cardiac plexus, cardiac and extracardiac nerves and neural ganglia. Bmp2 is dynamically regulated in the developing heart. 3'UTR-mediated mechanisms that restrain BMP2 synthesis may be relevant to congenital heart and vasculature malformations and to adult diseases involving aberrant BMP2 synthesis.
authors.affiliation: Department of Cell Biology, University of Medicine and Dentistry (UMDNJ)-New Jersey Medical School (NJMS), Newark, New Jersey, USA.
authors.forename: Boudewijn P T
authors.initials: BP
authors.lastname: Kruithof
authors.forename: Junwang
authors.initials: J
authors.lastname: Xu
authors.forename: David T
authors.initials: DT
authors.lastname: Fritz
authors.forename: Carolina S
authors.initials: CS
authors.lastname: Cabral
authors.forename: Vinciane
authors.initials: V
authors.lastname: Gaussin
authors.forename: Melissa B
authors.initials: MB
authors.lastname: Rogers
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D017124:Conserved Sequence; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D006321:Heart / Q000196:embryology / Q000294:innervation / Q000502:physiology*; D007150:Immunohistochemistry; D019426:Integrases / Q000378:metabolism; D007763:Lac Operon; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics / Q000378:metabolism; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism; D010496:Pericardium / Q000166:cytology / Q000196:embryology / Q000378:metabolism* / Q000502:physiology; D011499:Protein Processing, Post-Translational; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D017384:Sequence Deletion; D014158:Transcription, Genetic; D014162:Transfection; D019076:Transgenes
chemical_list: D020413:3' Untranslated Regions; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D016900:Neurofilament Proteins; C061195:neurofilament protein M; C045073:Cre recombinase; D019426:Integrases