Other
14 Authors
- Castillo M,
- Schwartz RJ,
- DiPersio CM,
- Wu M,
- Lu Y,
- Burns AR,
- Kumar A,
- Xiao Y,
- Nusrat A,
- Zhao L,
- Gunaratne P,
- Miao L,
- Liu Y,
- Guo H
| First Author | Miao L | Year | 2024 |
| Journal | Cardiovasc Res | Volume | 120 |
| Issue | 11 | Pages | 1279-1294 |
| PubMed ID | 38794925 | Mgi Jnum | J:354189 |
| Mgi Id | MGI:7733239 | Doi | 10.1093/cvr/cvae111 |
| Citation | Miao L, et al. (2024) beta1 integrins regulate cellular behaviour and cardiomyocyte organization during ventricular wall formation. Cardiovasc Res 120(11):1279-1294 |
| abstractText | AIMS: The mechanisms regulating the cellular behaviour and cardiomyocyte organization during ventricular wall morphogenesis are poorly understood. Cardiomyocytes are surrounded by extracellular matrix (ECM) and interact with ECM via integrins. This study aims to determine whether and how beta1 integrins regulate cardiomyocyte behaviour and organization during ventricular wall morphogenesis in the mouse. METHODS AND RESULTS: We applied mRNA deep sequencing and immunostaining to determine the expression repertoires of alpha/beta integrins and their ligands in the embryonic heart. Integrin beta1 subunit (beta1) and some of its ECM ligands are asymmetrically distributed and enriched in the luminal side of cardiomyocytes, and fibronectin surrounds cardiomyocytes, creating a network for them. Itgb1, which encodes the beta1, was deleted via Nkx2.5Cre/+ to generate myocardial-specific Itgb1 knockout (B1KO) mice. B1KO hearts display an absence of a trabecular zone but a thicker compact zone. The levels of hyaluronic acid and versican, essential for trabecular initiation, were not significantly different between control and B1KO. Instead, fibronectin, a ligand of beta1, was absent in the myocardium of B1KO hearts. Furthermore, B1KO cardiomyocytes display a random cellular orientation and fail to undergo perpendicular cell division, be organized properly, and establish the proper tissue architecture to form trabeculae. Mosaic clonal lineage tracing showed that Itgb1 regulates cardiomyocyte transmural migration and proliferation autonomously. CONCLUSION: beta1 is asymmetrically localized in the cardiomyocytes, and some of its ECM ligands are enriched along the luminal side of the myocardium, and fibronectin surrounds cardiomyocytes. beta1 integrins are required for cardiomyocytes to attach to the ECM network. This engagement provides structural support for cardiomyocytes to maintain shape, undergo perpendicular division, and establish cellular organization. Deletion of Itgb1 leads to loss of beta1 and fibronectin and prevents cardiomyocytes from engaging the ECM network, resulting in failure to establish tissue architecture to form trabeculae. |
