The Chordate Origins of Heart Regeneration

Abstract

The human heart is infamous for not healing after infarction in adults, prompting biomedical interest in species that can regenerate damaged hearts. In such animals as zebrafish and neonatal mice, cardiac repair relies on remaining heart tissue supporting cardiomyocyte proliferation. Natural de novo cardiogenesis in post-embryonic stages thus remains elusive. Here we show that the tunicate Ciona, an ascidian among the closest living relatives to the vertebrates, can survive complete chemogenetic ablation of the heart and loss of cardiac function, and recover both cardiac tissue and contractility. As in vertebrates, Ciona heart regeneration relies on Bone Morphogenetic Protein (BMP) signaling-dependent proliferation of cardiomyocytes, providing insights into the evolutionary origins of regenerative cardiogenesis in chordates. Remarkably, prospective lineage tracing by photoconversion of the fluorescent protein Kaede suggested that new cardiomyocytes can emerge from endodermal lineages in post-metamorphic animals, providing an unprecedented case of regenerative de novo cardiogenesis. Finally, while embryos cannot compensate for early losses of the cardiogenic lineage, forming heartless juveniles, developing animals gain their regenerative ability during metamorphosis, uncovering a fundamental transition between deterministic embryogenesis and regulative post-embryonic development.

Axis reset is rate limiting for onset of whole-body regenerative abilities during planarian development

“…Juvenile sponges 22 , crinoid larvae 24,25 , and annelid Capitella teleta larvae 26 have all been reported to have more limited regeneration abilities than adults of the same species. The tunicate Ciona intestinalis, a close relative of vertebrates, fails to regenerate structures as larvae that adults are capable of regenerating, such as the heart and neural complex 20,27 . Even within vertebrates, some lizard species that are capable of adult tail regeneration do not undergo proper tail regeneration in earlier developmental stages 28 .…”