Tropomyosin is required for cardiac morphogenesis, myofibril assembly, and formation of adherens junctions in the developing mouse embryo

Authors

  • Caroline R. McKeown,

    1. Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California
    Current affiliation:
    1. Department of Cellular and Molecular Neuroscience, The Scripps Research Institute, La Jolla, California
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  • Roberta B. Nowak,

    1. Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California
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  • David S. Gokhin,

    1. Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California
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  • Velia M. Fowler

    Corresponding author
    1. Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California
    • Correspondence to: Velia M. Fowler, PhD, Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 N Torrey Pines Road, CB163, La Jolla, CA 92037. E-mail: velia@scripps.edu

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  • The authors declare no competing financial interests.

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. Developmental Dynamics 243:800–817, 2014. © 2014 Wiley Periodicals, Inc.

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