Nerve injury activates transcriptional mechanisms that reprogram Schwann cells and neurons to generate cells, which are specialised to promote repair. Schwann cells abandon their normal functions relating to axonal ensheathment of and myelination and convert to repair Schwann cells tailored to support regeneration. Similarly, neurons activate regeneration associated genes (RAGs) and switch from signalling mode to growth mode. We find that activation of the transcription factor c-Jun in Schwann cells has an important role in both of these reprogramming events, and that Schwann cell c-Jun is therefore a central regulator of nerve regeneration. In the nerve distal to the injury, injury-induced expression of c-Jun in Schwann cells governs major aspects of Wallerian degeneration, the complex cellular events that allow cut axons to re-grow. c-Jun has two key functions in the response of Schwann cells to injury. First, and most importantly, it activates a repair program in Schwann cells. This includes (i) the expression of trophic factors, including GDNF and BDNF, and adhesion molecules that control neuronal survival and axon re-growth, (ii) the formation of regeneration tracks (Bungner bands) that lead axons back to their targets, and (iii) breakdown of myelin sheaths. Second, it accelerates the extinction of myelin gene expression (dedifferentiation) that is an important consequence of nerve damage and axonal degeneration. In this way Schwann cell c-Jun controls the conversion of myelin and non-myelin (Remak) Schwann cells to an alternative Schwann cell phenotype, the repair (Bungner) Schwann cell that is specialized to support nerve repair (Arthur-Farraj et al. Neuron 75: 633-47, 2012). Conditional inactivation of c-Jun in Schwann cells only results in the formation of a dysfunctional repair cell and failure of functional recovery. In the nerve proximal to the injury, Schwann cell c-Jun is also activated near the site of damage although the axons in this region do not degenerate. We present evidence that this proximal Schwann cell c-Jun expression is involved in activating regeneration activated genes in injured neurons, and regulates the switching of neurons from signalling to growth mode. This represents a novel and significant mechanism by which c-Jun controls nerve regeneration. Thus c-Jun dependent mechanisms in Schwann cells control regeneration in two distinct ways: by governing the generation of repair Schwann cells distal to the injury and by determining the intrinsic growth state of the damaged neurons. Myelin breakdown in injured nerves is carried out, first, by Schwann cells, and subsequently by macrophages that gradually invade damaged nerves. During the first 5-7 days after nerve injury, the Schwann cells themselves clear about 50% of the redundant myelin. Although this is thought to be important for regeneration, the cellular and molecular mechanisms of Schwann cell mediated myelin breakdown have not been established. We find that autophagy, a mechanism by which many cells digest their intrinsic cellular components, plays a central role in Schwann cell myelin breakdown. We show that nerve injury triggers strong activation of Schwann cell autophagy, find myelin debris in autophagosomes, show that autophagy of myelin is promoted by c-Jun and demonstrate a strong requirement for autophagy in myelin digestion, revealing a novel form of selective autophagy of the myelin sheath, myelinophagy (Gomez-Sanches, Carty et al J. Cell Biology, in press).The broader role of myelinopagy in Schwann cell biology, including regeneration and demyelinating disease remains to be established.