Differential Roles of Moesin and VASP in β-catenin-Associated Networks During Zebrafish Heart Regeneration

With cardiovascular disease remaining as the leading cause of mortality worldwide, it is largely due to the limited regenerative capacity of the human heart. However, zebrafish (Danio rerio) can fully regenerate cardiac tissue following injury, providing a valuable model for studying the mechanisms of heart repair. To investigate these mechanisms, we used proteomics methods in the past. Proximity labeling is a technique that identifies proteins based on their physical proximity to a protein of interest. It can be applied in organisms and in living cells (Roux et al., 2012; Cho et al., 2020). We used proximity labeling to characterize protein networks involved in heart regeneration. Β-catenin was chosen as bait protein because of its role in Wnt signaling and cell adhesion, leading to the identification of associated cytoskeletal and adhesion-related proteins. This study has shown that β-catenin-associated protein networks enriched in cytoskeletal and adhesion-related proteins can regenerate. My study aims to investigate the subcellular dynamics of two protein candidates, Moesin and vasodilator-stimulated phosphoprotein (VASP), during zebrafish heart regeneration. The Immunofluorescence showed that Moesin expression was significantly increased in the cardiomyocyte-rich regions following the injury, with signals appearing more localized in punctate structures. However, VASP showed a non-significant decrease in both cardiomyocyte and vascular regions. Neither protein exhibited significant changes in blood vessels. At the cardiomyocyte-endothelial cell (CM-EC) interface, Moesin signal was more prominent in injured hearts, whereas VASP remained unchanged. All the findings suggest that cytoskeletal remodeling during zebrafish heart regeneration is highly selective and may involve differential regulation of β-catenin-associated proteins. Moesin plays a role in the structural reorganization of cardiomyocytes during regeneration, while VASP appears to be less dynamically regulated. Understanding how these protein levels change may provide insight into the mechanisms that could be targeted in order to enhance cardiac repair in humans in the future.