Cd248a regulates pericyte development and viability in zebrafish.

Abstract

CD248 is a pericyte marker during embryonic and tumor neovascularization. Although its expression pattern and function in mammalian pericytes have been extensively studied, its role in zebrafish pericytes remains largely unexplored. In this study, we identify that among the two zebrafish orthologs of human CD248, cd248a, rather than cd248b, is predominantly expressed in pericytes during embryonic development. We generate cd248a and cd248b mutant zebrafish (cd248a^cc11/cc11 and cd248b^cc12/cc12) and observe a significant reduction in pericyte numbers in cd248a^cc11/cc11 mutants, accompanied by disruption of the blood-brain barrier. Notably, treatment with AG1295, a platelet-derived growth factor receptor inhibitor, attenuates the increase in pericyte proliferation induced by cd248a overexpression. Additionally, we find that CoCl₂-induced pericyte apoptosis is enhanced in cd248a^cc11/cc11 larvae, indicating that cd248a provides protection against hypoxia-induced apoptosis. Taken together, our findings elucidate the role and underlying mechanisms of cd248a in regulating pericyte proliferation and apoptosis in zebrafish.