Figure 10.

Figure 10.

Model of Midkine-a-mediated cell cycle regulation in Müller glia. A, In quiescent Müller glia, cell cycle inhibitors keep cells in G₀ phase. B, Injury induces cytokines and growth factors to upregulate regeneration-associated reprogramming genes for dedifferentiation and cell cycle reentry. Midkine-a-Alk signaling participates in the induction of the regeneration-associated gene, ascl1a, via phosphorylation of Stat3. Midkine-a signaling also induces expression of the cell cycle regulator, id2a, that inhibits cell cycle inhibitors, such as p130. C, In the absence of Midkine-a, Müller glia fail to suppress cell cycle inhibition, resulting in compromised progression of the cell cycle.