ABSTRACT
Tissue regenerative potential displays striking divergence across phylogeny and ontogeny, but the underlying mechanisms remain enigmatic. Loss of mammalian cardiac regenerative potential correlates with cardiomyocyte cell-cycle arrest and polyploidization as well as the development of postnatal endothermy. We reveal that diploid cardiomyocyte abundance across 41 species conforms to Kleiber's law-the ¾-power law scaling of metabolism with bodyweight-and inversely correlates with standard metabolic rate, body temperature, and serum thyroxine level. Inactivation of thyroid hormone signaling reduces mouse cardiomyocyte polyploidization, delays cell-cycle exit, and retains cardiac regenerative potential in adults. Conversely, exogenous thyroid hormones inhibit zebrafish heart regeneration. Thus, our findings suggest that loss of heart regenerative capacity in adult mammals is triggered by increasing thyroid hormones and may be a trade-off for the acquisition of endothermy.
Subject(s)
Heart/physiology , Myocytes, Cardiac/physiology , Polyploidy , Regeneration/physiology , Thyroid Hormones/physiology , Animals , Body Temperature Regulation , Cell Cycle Checkpoints , Cell Proliferation , Diploidy , Mice , Myocytes, Cardiac/classification , Phylogeny , Receptors, Thyroid Hormone/genetics , Receptors, Thyroid Hormone/physiology , Regeneration/drug effects , Regeneration/genetics , Signal Transduction , Thyroid Hormones/pharmacology , ZebrafishABSTRACT
Muscles are traditionally considered in the context of force generation. Scimone et al. (2017), reporting in Nature, now examine muscles in a developmental setting and find unexpected roles for distinct planarian muscle fibers. The authors show that muscles provide patterning signals to promote regeneration and guide tissue growth after injury.
