| First Author | McKeown CR | Year | 2014 |
| Journal | Dev Dyn | Volume | 243 |
| Issue | 6 | Pages | 800-17 |
| PubMed ID | 24500875 | Mgi Jnum | J:211921 |
| Mgi Id | MGI:5576983 | Doi | 10.1002/dvdy.24115 |
| Citation | McKeown CR, et al. (2014) Tropomyosin is required for cardiac morphogenesis, myofibril assembly, and formation of adherens junctions in the developing mouse embryo. Dev Dyn 243(6):800-17 |
| abstractText | 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 alphaTM1, the major striated muscle TM isoform. RESULTS: Mice lacking alphaTM1 are embryonic lethal at E9.5 with enlarged, misshapen, and non-beating hearts characterized by an abnormally thin myocardium and reduced trabeculae. alphaTM1-deficient cardiomyocytes do not assemble striated myofibrils, instead displaying aberrant non-striated F-actin fibrils with alpha-actinin puncta dispersed irregularly along their lengths. alphaTM1'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 alphaTM1-deficient cardiomyocytes, alpha-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 alpha-actinin/F-actin adherens belt assembly. CONCLUSIONS: Absence of alphaTM1 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 alphaTM1/Tmod1-based pathway stabilizing F-actin at cell-cell junctions, which may be required for maintenance of cell shapes during embryonic cardiac morphogenesis. |
