Tumor Suppressor TSC1 Negatively Regulates Polo-like Kinase Expression and Controls the Balance of Schwann Cell Proliferation and Differentiation

Activation of mTOR signaling by Tsc1 ablation during early developmental stages increases SC proliferation and delays radial sorting, while causing hypomyelination in the PNS. However, knockout Tsc1 in myelinating SCs at postnatal stages promotes myelin overgrowth and outfoldings. Sustained mTOR pathway leads to activation of the PLK signaling pathway. mTOR attenuation or pharmacological inhibition of PLK1 could partially rescue myelination defects in Tsc1 mutant sciatic nerves. Our data suggest that TSC1-mTOR maintains the homeostasis of SC proliferation and differentiation in a stage-specific manner. Gene expression profiling of sciatic nerve from P7 control and Tsc1cKO mice