High expression profiling analysis of the early response to spinal cord injury identified a key role for mTORC1 signaling

Xenopus laevis are able to regenerate the spinal cord during larvae stages through the activation of neural stem progenitor cells (NSPC). Here, we use high-resolution expression profiling to characterize the early transcriptome changes induced after spinal cord injury, and identify the signals that trigger NSPC proliferation. The analysis delineates a pathway that starts with a rapid and transitory activation of immediate early genes, followed by migration processes and immune response genes, the pervasive increase of NSPC specific ribosome biogenesis factors, and genes involved in stem cell proliferation. Western blot and immunofluorescence analysis showed that mTORC1 is rapidly and transiently activated after SCI, and its pharmacological inhibition impairs spinal cord regeneration, and proliferation of NSPC of genes involved in the G1/S transition of cell cycle, with a strong effect on PCNA. We propose that the mTOR signaling pathway is a key player in the activation of NPSCs during the early steps of spinal cord regeneration. Overall design: Time-series analysis of the early transcriptional changes deployed in response to spinal cord injury in regenerative stage of Xenopus laevis.