title: Expression and function of alpha-smooth muscle actin during embryonic-stem-cell-derived cardiomyocyte differentiation.
abstract: Three alpha-muscle actin isoforms are sequentially expressed during in vivo cardiac development. alpha-Smooth muscle actin is first and transiently expressed, followed by alpha-skeletal and finally alpha-cardiac actin. The significance of these transitions in actin gene expression during myogenesis remains to be determined. To understand whether actin isoforms have specific functions during cardiac development and cardiomyocyte contractility, we have hampered alpha-smooth muscle and alpha-skeletal actin expression and organization during embryonic stem cell differentiation towards cardiomyocyte. We show that the sequence of actin isoform expression displays similar pattern in the in vitro model and in mouse heart embryogenesis. Treatment with an interfering fusion peptide containing the N-terminal sequence of alpha-smooth muscle actin during a time window preceding spontaneous beating, prevents proper cardiac sarcomyogenesis, whereas alpha-skeletal actin-fusion peptide has no effect. Knockdown of alpha-smooth muscle actin in embryonic stem cells using RNA interference also affects cardiac differentiation. The application of both fusion peptides on beating embryoid bodies impairs frequency. These results suggest specific functional activities for actin isoforms in cardiogenesis and cardiomyocyte contractility.
authors.affiliation: Department of Geriatrics, Laboratory of Ageing, Geneva Hospital, Chêne-Bourg, Geneva, Switzerland. sophie.clement@medecine.unige.ch
authors.forename: Sophie
authors.initials: S
authors.lastname: Clément
authors.forename: Michael
authors.initials: M
authors.lastname: Stouffs
authors.forename: Esther
authors.initials: E
authors.lastname: Bettiol
authors.forename: Sandy
authors.initials: S
authors.lastname: Kampf
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Krause
authors.forename: Christine
authors.initials: C
authors.lastname: Chaponnier
authors.forename: Marisa
authors.initials: M
authors.lastname: Jaconi
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology*; D019084:Fluorescent Antibody Technique, Indirect; D005786:Gene Expression Regulation; D006321:Heart / Q000196:embryology; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000378:metabolism*; D009200:Myocardial Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000502:physiology*
chemical_list: D000199:Actins