Axon-dependent expression of YAP/TAZ mediates Schwann cell remyelination but not proliferation after nerve injury
Matthew Grove,
Hyunkyoung Lee,
Huaqing Zhao,
Young-Jin Son
Affiliations
Matthew Grove
Shriners Hospitals Pediatric Research Center and Center for Neural Repair and Rehabilitation, Temple University, Philadelphia, United States; Department of Anatomy and Cell Biology, Temple University, Philadelphia, United States
Hyunkyoung Lee
Shriners Hospitals Pediatric Research Center and Center for Neural Repair and Rehabilitation, Temple University, Philadelphia, United States; Department of Anatomy and Cell Biology, Temple University, Philadelphia, United States
Huaqing Zhao
Department of Clinical Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, United States
Shriners Hospitals Pediatric Research Center and Center for Neural Repair and Rehabilitation, Temple University, Philadelphia, United States; Department of Anatomy and Cell Biology, Temple University, Philadelphia, United States
Previously we showed that YAP/TAZ promote not only proliferation but also differentiation of immature Schwann cells (SCs), thereby forming and maintaining the myelin sheath around peripheral axons (Grove et al., 2017). Here we show that YAP/TAZ are required for mature SCs to restore peripheral myelination, but not to proliferate, after nerve injury. We find that YAP/TAZ dramatically disappear from SCs of adult mice concurrent with axon degeneration after nerve injury. They reappear in SCs only if axons regenerate. YAP/TAZ ablation does not impair SC proliferation or transdifferentiation into growth promoting repair SCs. SCs lacking YAP/TAZ, however, fail to upregulate myelin-associated genes and completely fail to remyelinate regenerated axons. We also show that both YAP and TAZ are redundantly required for optimal remyelination. These findings suggest that axons regulate transcriptional activity of YAP/TAZ in adult SCs and that YAP/TAZ are essential for functional regeneration of peripheral nerve.
