The post-mitotic nature of adult human cardiomyocytes means that our risk of heart tumours is low. By contrast, adult zebrafish hearts can undergo cardiomyocyte proliferation to regenerate damaged tissue, but it is unknown if they respond to oncogene expression. Here, Anna Jaźwińska and colleagues generate a zebrafish model for reversibly inducing expression of the HRASG12V oncogene in zebrafish cardiomyocytes. They find that HRASG12V overexpression results in enlarged hearts and increased activation of the kinase TOR. This enlarged heart phenotype can be rescued by inhibiting TOR signalling using rapamycin. They use RNA sequencing to identify genes that are dysregulated in HRASG12V hearts and are returned to nearly normal expression levels by rapamycin treatment. Over 2000 of these genes are similarly dysregulated in regenerating zebrafish hearts, suggesting that regeneration and oncogene-induced proliferation share some common pathways. Indeed, the authors find that transient expression of HRASG12V in hearts prior to injury results in increased cardiomyocyte dedifferentiation and proliferation, ultimately leading to a reduction in wound area without an increase in ventricle size. Overall, this work compares oncogene-induced proliferation and regeneration in the same model system to uncover similarities between these two processes.
