title: Tropomyosin is required for cardiac morphogenesis, myofibril assembly, and formation of adherens junctions in the developing mouse embryo.
abstract: BACKGROUND
  We explored a function for tropomyosin (TM) in mammalian myofibril assembly and cardiac development by analyzing a deletion in the mouse TPM1 gene targeting αTM1, the major striated muscle TM isoform.
  
  
  RESULTS
  Mice lacking αTM1 are embryonic lethal at E9.5 with enlarged, misshapen, and non-beating hearts characterized by an abnormally thin myocardium and reduced trabeculae. αTM1-deficient cardiomyocytes do not assemble striated myofibrils, instead displaying aberrant non-striated F-actin fibrils with α-actinin puncta dispersed irregularly along their lengths. αTM1's binding partner, tropomodulin1 (Tmod1), is also disorganized, and both myomesin-containing thick filaments as well as titin Z1Z2 fail to assemble in a striated pattern. Adherens junctions are reduced in size in αTM1-deficient cardiomyocytes, α-actinin/F-actin adherens belts fail to assemble at apical cell-cell contacts, and cell contours are highly irregular, resulting in abnormal cell shapes and a highly folded cardiac surface. In addition, Tmod1-deficient cardiomyocytes exhibit failure of α-actinin/F-actin adherens belt assembly.
  
  
  CONCLUSIONS
  Absence of αTM1 resulting in unstable F-actin may preclude sarcomere formation and/or lead to degeneration of partially assembled sarcomeres due to unregulated actomyosin interactions. Our data also identify a novel αTM1/Tmod1-based pathway stabilizing F-actin at cell-cell junctions, which may be required for maintenance of cell shapes during embryonic cardiac morphogenesis.
authors: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California.
authors: Caroline R
authors: CR
authors: McKeown
authors: Roberta B
authors: RB
authors: Nowak
authors: David S
authors: DS
authors: Gokhin
authors: Velia M
authors: VM
authors: Fowler
mesh_terms: D022005:Adherens Junctions / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology*; D006321:Heart / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis / Q000502:physiology*; D014335:Tropomyosin / Q000235:genetics / Q000378:metabolism*
chemical_list: C490774:Tpm1 protein, mouse; D014335:Tropomyosin
keywords: cardiomyocyte; cell junction; heart; myofibrillogenesis; myomesin; thin filament; titin; tropomodulin1; α-actinin