| First Author | Lim JA | Year | 2014 |
| Journal | Cardiovasc Res | Volume | 101 |
| Issue | 1 | Pages | 39-47 |
| PubMed ID | 24064296 | Mgi Jnum | J:219548 |
| Mgi Id | MGI:5621128 | Doi | 10.1093/cvr/cvt222 |
| Citation | Lim JA, et al. (2014) Loss of beta2-spectrin prevents cardiomyocyte differentiation and heart development. Cardiovasc Res 101(1):39-47 |
| abstractText | AIMS: beta2-Spectrin is an actin-binding protein that plays an important role in membrane integrity and the transforming growth factor (TGF)-beta signalling pathway as an adaptor for Smads. Loss of beta2-spectrin in mice (Spnb2(-/-)) results in embryonic lethality with gastrointestinal, liver, neural, and heart abnormalities that are similar to those in Smad2(+/-)Smad3(+/-) mice. However, to date, the role of beta2-spectrin in embryogenesis, particularly in heart development, has been poorly delineated. Here, we demonstrated that beta2-spectrin is required for the survival and differentiation of cardiomyocytes, and its loss resulted in defects in heart development with failure of ventricular wall thickening. METHODS AND RESULTS: Disruption of beta2-spectrin in primary muscle cells not only inhibited TGF-beta/Smad signalling, but also reduced the expression of the cardiomyocyte differentiation markers Nkx2.5, dystrophin, and alpha-smooth muscle actin (alpha-SMA). Furthermore, cytoskeletal networks of dystrophin, F-actin, and alpha-SMA in cardiomyocytes were disorganized upon loss of beta2-spectrin. In addition, deletion of beta2-spectrin in mice (Spnb2(tm1a/tm1a)) prevented proper development of the heart in association with disintegration of dystrophin structure and markedly reduced survival. CONCLUSION: These data suggest that beta2-spectrin deficiency leads to inactivation of TGF-beta/Smad signalling and contributes to dysregulation of the cell cycle, proliferation, differentiation, and the cytoskeletal network, and it leads to defective heart development. Our data demonstrate that beta2-spectrin is required for proper development of the heart and that disruption of beta2-spectrin is a potential underlying cause of congenital heart defects. |
