Human Specifically Inhibits Epimorphic Regeneration in the Zebrafish Heart

The Alternative Reading Frame (ARF) protein is a tumor suppressor encoded by the gene in mammals but not lower regenerative vertebrates, and has been previously implicated as a context-sensitive suppressor of regeneration in murine skeletal muscle and humanized ARF-expressing zebrafish fins. This study extends our investigation of the role of ARF in the regeneration of other solid tissues, including the zebrafish heart and the mammalian digit. Heart regeneration after cryoinjury was used to mimic massive myocardial infarction. gene expression was upregulated during the cardiac regenerative process and slowed the rate of morphological recovery. specifically impacts cardiomyocytes, neovascularization, and the endothelial-mesenchymal transition, while not affecting epicardial proliferation. This suggests that in the context of regeneration, is specifically expressed in cells undergoing dedifferentiation. To investigate as a suppressor of epimorphic regeneration in mammalian systems, we also tested whether the absence of was permissive for murine digit regeneration, but found that absence alone was insufficient to significantly alter digit restoration. These findings provide additional evidence that suppresses epimorphic regeneration, but suggests that modulation of alone is insufficient to permit regeneration.