LAUSR

Zebrafish hearts can regenerate by replacing damaged tissue with new cardiomyocytes. Although the steps leading up to the proliferation of surviving cardiomyocytes have been extensively studied, little is known about the mechanisms that control proliferation and redifferentiation to a mature state. We found that the cardiac dyad, a structure that regulates calcium handling and excitation-contraction coupling, played a key role in the redifferentiation process. A component of the cardiac dyad called leucine-rich repeat–containing 10 (Lrrc10) acted as a negative regulator of proliferation, prevented cardiomegaly, and induced redifferentiation. We found that its function was conserved in mammalian cardiomyocytes. This study highlights the importance of the underlying mechanisms required for heart regeneration and their application to the generation of fully functional cardiomyocytes. Description Editor’s summary Unlike mammals, some animal species such as zebrafish can regenerate their heart after injury by using their surviving cardiomyocytes to produce new cells. It is unclear how these cells stop dividing and mature enough to contribute to heart function. Nguyen et al. used ex vivo imaging to visualize intracellular calcium dynamics in the regenerating zebrafish heart to study cardiomyocyte maturation. The formation of the cardiac dyad, a structure responsible for regulating intracellular calcium handling, played a critical role in determining whether cardiomyocytes proliferated or progressed through maturation. Furthermore, LRRC10, a component of the cardiac dyad, was implicated in the regulation of cardiomyocyte maturation in zebrafish, mouse, and humans. —Stella M. Hurtley The Lrrc10 protein is important in determining whether cardiomyocytes proliferate or progress through to maturation.