title: Epicardium is required for sarcomeric maturation and cardiomyocyte growth in the ventricular compact layer mediated by transforming growth factor β and fibroblast growth factor before the onset of coronary circulation.
abstract: The epicardium, which is derived from the proepicardial organ (PE) as the third epithelial layer of the developing heart, is crucial for ventricular morphogenesis. An epicardial deficiency leads to a thin compact layer for the developing ventricle; however, the mechanisms leading to the impaired development of the compact layer are not well understood. Using chick embryonic hearts, we produced epicardium-deficient hearts by surgical ablation or blockade of the migration of PE and examined the mechanisms underlying a thin compact myocardium. Sarcomeric maturation (distance between Z-lines) and cardiomyocyte growth (size) were affected in the thin compact myocardium of epicardium-deficient ventricles, in which the amounts of phospho-smad2 and phospho-ERK as well as expression of transforming growth factor (TGF)β2 and fibroblast growth factor (FGF)2 were reduced. TGFβ and FGF were required for the maturation of sarcomeres and growth of cardiomyocytes in cultured ventricles. In ovo co-transfection of dominant negative (dN)-Alk5 (dN-TGFβ receptor I) and dN-FGF receptor 1 to ventricles caused a thin compact myocardium. Our results suggest that immature sarcomeres and small cardiomyocytes are the causative architectures of an epicardium-deficient thin compact layer and also that epicardium-dependent signaling mediated by TGFβ and FGF plays a role in the development of the ventricular compact layer before the onset of coronary circulation.
authors.affiliation: Department of Anatomy and Cell Biology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamagishi
authors.forename: Mayu
authors.initials: M
authors.lastname: Narematsu
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kamimura
authors.forename: Masatake
authors.initials: M
authors.lastname: Kai
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakajima
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000378:metabolism; D049108:Cell Enlargement; D049109:Cell Proliferation; D002642:Chick Embryo; D003331:Coronary Vessels / Q000196:embryology* / Q000502:physiology; D005346:Fibroblast Growth Factors / Q000502:physiology*; D006352:Heart Ventricles / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000502:physiology*; D010496:Pericardium / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D012039:Regional Blood Flow; D012518:Sarcomeres / Q000502:physiology; D046509:Tissue Culture Techniques; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D030161:Avian Proteins; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D005346:Fibroblast Growth Factors; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I
keywords: compact myocardium; epicardium; fibroblast growth factor; transforming growth factor β; ventricular non-compaction