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Interplay between calcium and sarcomeres directs cardiomyocyte maturation during regeneration (Science, 2023 May)

Images of fish and their hearts reveal that wild-type and GFP-Lrrc10 OE fish have comparably sized hearts. ca-Vdra OE shows cardiomegaly, which is rescued when fish coexpress Lrrc10

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.

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