CCBE1 Is Essential for Epicardial Function during Myocardium Development
The epicardium is a single cell layer of mesothelial cells that plays a critical role during heart development contributing to different cardiac cell types of the developing heart through epithelial-to-mesenchymal transition (EMT). Moreover, the epicardium is a source of secreted growth factors that...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/20/12642 |
| Summary: | The epicardium is a single cell layer of mesothelial cells that plays a critical role during heart development contributing to different cardiac cell types of the developing heart through epithelial-to-mesenchymal transition (EMT). Moreover, the epicardium is a source of secreted growth factors that promote myocardial growth. CCBE1 is a secreted extracellular matrix protein expressed by epicardial cells that is required for the formation of the primitive coronary plexus. However, the role of CCBE1 during epicardial development was still unknown. Here, using a <i>Ccbe1</i> knockout (KO) mouse model, we observed that loss of CCBE1 leads to congenital heart defects including thinner and hyper-trabeculated ventricular myocardium. In addition, <i>Ccbe1</i> mutant hearts displayed reduced proliferation of cardiomyocyte and epicardial cells. Epicardial outgrowth culture assay to assess epicardial-derived cells (EPDC) migration showed reduced invasion of the collagen gel by EPDCs in <i>Ccbe1</i> KO epicardial explants. <i>Ccbe1</i> KO hearts also displayed fewer nonmyocyte/nonendothelial cells intramyocardially with a reduced proliferation rate. Additionally, RNA-seq data and experimental validation by qRT-PCR showed a marked deregulation of EMT-related genes in developing <i>Ccbe1</i> mutant hearts. Together, these findings indicate that the myocardium defects in <i>Ccbe1</i> KO mice arise from disruption of epicardial development and function. |
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| ISSN: | 1661-6596 1422-0067 |