1. TFEB/3 Govern Repair Schwann Cell Generation and Function Following Peripheral Nerve Injury.
- Author
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Patel AA, Kim H, Ramesh R, Marquez A, Faraj MM, Antikainen H, Lee AS, Torres A, Khawaja IM, Heffernan C, Bonder EM, Maurel P, Svaren J, Son YJ, Dobrowolski R, and Kim HA
- Subjects
- Animals, Mice, Male, Female, Autophagy physiology, Mice, Inbred C57BL, Sciatic Nerve injuries, Schwann Cells metabolism, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors metabolism, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors genetics, Peripheral Nerve Injuries metabolism, Nerve Regeneration physiology, Nerve Regeneration genetics, Mice, Knockout
- Abstract
TFEB and TFE3 (TFEB/3), key regulators of lysosomal biogenesis and autophagy, play diverse roles depending on cell type. This study highlights a hitherto unrecognized role of TFEB/3 crucial for peripheral nerve repair. Specifically, they promote the generation of progenitor-like repair Schwann cells after axonal injury. In Schwann cell-specific TFEB/3 double knock-out mice of either sex, the TFEB/3 loss disrupts the transcriptomic reprogramming that is essential for the formation of repair Schwann cells. Consequently, mutant mice fail to populate the injured nerve with repair Schwann cells and exhibit defects in axon regrowth, target reinnervation, and functional recovery. TFEB/3 deficiency inhibits the expression of injury-responsive repair Schwann cell genes, despite the continued expression of c -jun , a previously identified regulator of repair Schwann cell function. TFEB/3 binding motifs are enriched in the enhancer regions of injury-responsive genes, suggesting their role in repair gene activation. Autophagy-dependent myelin breakdown is not impaired despite TFEB/3 deficiency. These findings underscore a unique role of TFEB/3 in adult Schwann cells that is required for proper peripheral nerve regeneration., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)
- Published
- 2024
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