We are investigating molecular mechanisms governing cell plasticity and cell proliferation-quiescence decision. The decision for cells to proliferate or not plays key roles in development, tissue repair, and regeneration. We have developed a zebrafish model, in which a population of quiescent cells can be induced to reenter the cell cycle and proliferate. Using this whole animal platform, in vivo imaging, CRISPR/Cas9 gene editing, chemical biology, and RNAseq analyses have led to the discovery of a number of key regulators governing the cell quiescence-proliferation decision. Many of them are converged onto the insulin/insulin-like growth factor (IIS)-PI3 kinase-Akt-mTor signaling pathway.