Stab injury to the CNS damages glial cells and axons. Glial cells in the vicinity of the damage site up-regulate JNK signaling and thereby formation of the AP1 transcription heterodimer. In addition, Rac1/ Rho signalling activation by small GTPases results in cytoskeleton remodeling and increased Draper expression. Draper activation and debris engulfment depends on phosphorylation by Src42, Shark and the adaptor molecule Ced6. Draper activation up-regulates Pi3K signaling in adjacent undamaged neurons blocking axonal transport and hindering recovery. Damage also stimulates proliferation of glial cells. Ia-2 on neuronal membranes genetically interacts with Kon, the NG2 ortholog, on glia membranes. Activation of Ia-2 and Kon activates neuronal and glial secretion of Dilp6, which binds to InR on glia initiating insulin signaling and proliferation. In a subset of ensheathing glia cells that express the transcription factor repo, Insulin signaling drives Cyclin E, initiating division. Active Notch signaling promotes proliferation whereas nuclear incorporation of Pros terminates proliferation. In some astrocyte-like glia, insulin signaling initiates Dpn expression, a neural stem cell marker. Dpn positive cells divide to give rise to neurons and glia. The PDZ domain of Kon can be cleaved by alpha- and gamma-secretases into four different isoforms, of which two are part of a negative feedback loop repressing Notch signaling and activating Pros expression; AP1, activator protein 1; Dilp6, Drosophila insulin like peptide 6; Dpn, Deadpan; Ia-2, Islets antigen-2; InR, Insulin receptor; JNK, c-jun n-terminal kinase; Kon, Kon-tiki; NG2, Neural glia antigen 2; Pros, Prospero; Repo, Reverse polarity; Src42, Sarcoma 42