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Fig. 2 | BMC Systems Biology

Fig. 2

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

Fig. 2

Recalled-blastema-like regeneration strategy in the TGF-β signaling pathway for core proteins. We proposed a multiple-step recalled-blastema-like formation model, including injury response, de-differentiation, recalled-blastema-like formation, differentiation, and pattern formation steps. The length of the arrows in the figure indicates duration of activities during the regeneration process. The TGF-β signaling pathway is the primary pathway identified for core proteins, including Smad7, Smurf2, Jun, Mapk1, Mapk3, Map3k7, Smad3a, Skib, Smad2, and Spaw. Map3k7 removes excessively damaged cells and also augments the survival of slightly damaged cells in the injury response step. In the second step, a source of recalled-blastema-like formation is produced by Mapk1 and Mapk3, which promote proliferation and de-differentiation in undamaged cells, which is induced by impaired tissue. In the third step, Smad2 and Smad7 act as antagonists while Smurf2 promotes the expression of Smad7. They coordinate the accumulation of stem cells and recalled-blastema-like formation to prepare for differentiation and pattern formation in the next step. Jun and Smad3 regulate the G1 phase of the cell cycle and mediate cell fate while Skib and Spaw regulate pattern formation. The last step can be viewed as termination of the regeneration process. TGF-β participates in each step and is predicted to serve as the vital signal needed to carry out the regeneration process

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