The authors declare no competing financial interests.
Tropomyosin is required for cardiac morphogenesis, myofibril assembly, and formation of adherens junctions in the developing mouse embryo
Article first published online: 22 MAY 2014
© 2014 Wiley Periodicals, Inc.
Volume 243, Issue 6, page C1, June 2014
How to Cite
McKeown, C. R., Nowak, R. B., Gokhin, D. S. and Fowler, V. M. (2014), Tropomyosin is required for cardiac morphogenesis, myofibril assembly, and formation of adherens junctions in the developing mouse embryo. Dev. Dyn., 243: C1. doi: 10.1002/dvdy.24048
- Issue published online: 22 MAY 2014
- Article first published online: 22 MAY 2014
- Manuscript Accepted: 3 FEB 2014
- Manuscript Revised: 31 JAN 2014
- Manuscript Received: 9 JAN 2014
- NIH/NHLBI. Grant Numbers: R01-HL083464, T32-HL07695
- NIH/NIAMS. Grant Number: P30-AR061303
- George E. Hewitt Foundation for Medical Research
- Muscular Dystrophy Association
- NIH/NEI. Grant Number: P30-EY12598
- Cited By
- cell junction;
- thin filament;
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.