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Background  Regeneration is an important biological process for the restoration of organ mass, structure, and function after damage, and involves complex bio-physiological mechanisms including cell differentiation and immune responses. We constructed four regenerative protein-protein interaction (PPI) networks using dynamic models and AIC (Akaike’s Information Criterion), based on time-course microarray data from the regeneration of four  zebrafish  organs: heart, cerebellum, fin, and retina. We extracted core and organ-specific proteins, and proposed a recalled-blastema-like formation model to uncover regeneration strategies in  zebrafish .    Results  It was observed that the core proteins were involved in TGF-β signaling for each step in the recalled-blastema-like formation model and TGF-β signaling may be vital for regeneration. Integrins, FGF, and PDGF accelerate hemostasis during heart injury, while Bdnf shields retinal neurons from secondary damage and augments survival during the injury response. Wnt signaling mediates the growth and differentiation of cerebellum and fin neural stem cells, potentially providing a signal to trigger differentiation.    Conclusion  Through our analysis of all four  zebrafish  regenerative PPI networks, we provide insights that uncover the underlying strategies of  zebrafish  organ regeneration.

Uncovering the regeneration strategies of zebrafish organs: a comprehensive systems biology study on heart, cerebellum, fin, and retina regeneration