Mitf is a Schwann Cell Sensor of Axonal Integrity that Drives Nerve Repair

Here we identify Mitf as a transcriptional sensor of axon damage under the control of Nrg-ErbB-PI3K-PI5K-mTorc2 signaling. Mitf regulates a core transcriptional program for generating functional repair Schwann cells following injury and during peripheral neuropathies caused by CMT4J and CMT4D. In the absence of Mitf, core genes for epithelial-to-mesenchymal transition, metabolism and dedifferentiation are misexpressed and nerve repair is disrupted. Taken together, our findings demonstrate that Schwann cells monitor axonal health using a phosphoinositide signaling system that controls Mitf, which is critical for activating cellular plasticity and counteracting neural disease. We performed gene expression profiling analysis using data obtained from RNA-seq of sciatic nerves from Mitf mutant mice in both control and injury experiments as well as in Ndrg1 and Egr2Cre models mutants. Overall design: Comparative gene expression profiling analysis of RNA-seq data of sciatic nerves.