4.8 Article

Interplay between calcium and sarcomeres directs cardiomyocyte maturation during regeneration

Journal

SCIENCE
Volume 380, Issue 6646, Pages 758-764

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abo6718

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Zebrafish hearts can regenerate by replacing damaged tissue with new cardiomyocytes. The cardiac dyad, a structure that regulates calcium handling and excitation-contraction coupling, plays a key role in the redifferentiation process.
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 excitationcontraction 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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