Ccbe1, or collagen-and calcium-binding EGF-like domains 1, is a secreted protein. It is essential for lymphangiogenesis during development, enhancing VEGF-C signaling [1,3]. The VEGFC/VEGFR3 signaling pathway, in which Ccbe1 is involved, is crucial for lymphatic vessel formation during embryonic development, tissue regeneration, and tumor progression [3]. Moreover, Ccbe1 has emerged as significant in heart development and disease [1].

Using a Ccbe1 knockout (KO) mouse model, it was observed that loss of CCBE1 leads to congenital heart defects, including a thinner and hyper-trabeculated ventricular myocardium, reduced proliferation of cardiomyocyte and epicardial cells, and fewer nonmyocyte/nonendothelial cells intramyocardially with a reduced proliferation rate [2]. In addition, Ccbe1 mutant hearts showed deregulation of EMT-related genes [2]. Ccbe1 KO also inhibited coronary growth and led to defective dorsal and ventral intramyocardial vessels, as well as delayed and mispatterned coronary artery stem formation in mouse hearts [4].

In conclusion, Ccbe1 is vital for lymphangiogenesis and heart development. Findings from Ccbe1 KO mouse models have revealed its essential role in cardiac development, with implications for understanding congenital heart diseases. These models have provided insights into how Ccbe1 affects the structure and function of the heart, highlighting its significance in both normal development and disease-related processes [1,2,4].

References:

1. Bonet, Fernando, Inácio, José M, Bover, Oriol, Añez, Sabrina B, Belo, José A. 2022. CCBE1 in Cardiac Development and Disease. In Frontiers in genetics, 13, 836694. doi:10.3389/fgene.2022.836694. https://pubmed.ncbi.nlm.nih.gov/35222551/

2. Bonet, Fernando, Añez, Sabrina Brito, Inácio, José Manuel, Futschik, Matthias E, Belo, José Antonio. 2022. CCBE1 Is Essential for Epicardial Function during Myocardium Development. In International journal of molecular sciences, 23, . doi:10.3390/ijms232012642. https://pubmed.ncbi.nlm.nih.gov/36293499/

3. Le Guen, Ludovic, Karpanen, Terhi, Schulte, Dörte, Schulte-Merker, Stefan, Hogan, Benjamin M. 2014. Ccbe1 regulates Vegfc-mediated induction of Vegfr3 signaling during embryonic lymphangiogenesis. In Development (Cambridge, England), 141, 1239-49. doi:10.1242/dev.100495. https://pubmed.ncbi.nlm.nih.gov/24523457/

4. Bonet, Fernando, Pereira, Paulo N G, Bover, Oriol, Inácio, José M, Belo, José A. . CCBE1 is required for coronary vessel development and proper coronary artery stem formation in the mouse heart. In Developmental dynamics : an official publication of the American Association of Anatomists, 247, 1135-1145. doi:10.1002/dvdy.24670. https://pubmed.ncbi.nlm.nih.gov/30204931/