| First Author | Liu H | Year | 2023 |
| Journal | Life Sci Alliance | Volume | 6 |
| Issue | 9 | PubMed ID | 37385754 |
| Mgi Jnum | J:337546 | Mgi Id | MGI:7495140 |
| Doi | 10.26508/lsa.202302163 | Citation | Liu H, et al. (2023) beta-Catenin regulates endocardial cushion growth by suppressing p21. Life Sci Alliance 6(9) |
| abstractText | Endocardial cushion formation is essential for heart valve development and heart chamber separation. Abnormal endocardial cushion formation often causes congenital heart defects. beta-Catenin is known to be essential for endocardial cushion formation; however, the underlying cellular and molecular mechanisms remain incompletely understood. Here, we show that endothelial-specific deletion of beta-catenin in mice resulted in formation of hypoplastic endocardial cushions due to reduced cell proliferation and impaired cell migration. By using a beta-catenin (DM) allele in which the transcriptional function of beta-catenin is selectively disrupted, we further reveal that beta-catenin regulated cell proliferation and migration through its transcriptional and non-transcriptional function, respectively. At the molecular level, loss of beta-catenin resulted in increased expression of cell cycle inhibitor p21 in cushion endocardial and mesenchymal cells in vivo. In vitro rescue experiments with HUVECs and pig aortic valve interstitial cells confirmed that beta-catenin promoted cell proliferation by suppressing p21. In addition, one savvy negative observation is that beta-catenin was dispensable for endocardial-to-mesenchymal fate change. Taken together, our findings demonstrate that beta-catenin is essential for cell proliferation and migration but dispensable for endocardial cells to gain mesenchymal fate during endocardial cushion formation. Mechanistically, beta-catenin promotes cell proliferation by suppressing p21. These findings inform the potential role of beta-catenin in the etiology of congenital heart defects. |
