Abstract
The peripheral nervous system (PNS) regenerates after injury. However, regeneration is often compromised in the case of large lesions, and the speed of axon reconnection to their target is critical for successful functional recovery. After injury, mature Schwann cells (SCs) convert into repair cells that foster axonal regrowth, and redifferentiate to rebuild myelin. These processes require the regulation of several transcription factors, but the driving mechanisms remain partially understood. Here we identify an early response to nerve injury controlled by histone deacetylase 2 (HDAC2), which coordinates the action of other chromatin-remodelling enzymes to induce the upregulation of Oct6, a key transcription factor for SC development. Inactivating this mechanism using mouse genetics allows earlier conversion into repair cells and leads to faster axonal regrowth, but impairs remyelination. Consistently, short-term HDAC1/2 inhibitor treatment early after lesion accelerates functional recovery and enhances regeneration, thereby identifying a new therapeutic strategy to improve PNS regeneration after lesion.
Highlights
The peripheral nervous system (PNS) regenerates after injury
We previously showed that the chromatin-remodelling enzymes histone deacetylase (HDAC)[1] and histone deacetylase 2 (HDAC2) are essential for the specification of neural crest cells into peripheral glia[17], for Schwann cells (SCs) survival and myelination during postnatal development[18], and for the maintenance of PNS integrity in adults[20]
HDAC2 was SUMOylated in adult nerves (Fig. 1c) and SUMOylation was increased after lesion (Fig. 1a), suggesting modulation of HDAC2 activity, binding partners and/or stability[27] after lesion
Summary
The peripheral nervous system (PNS) regenerates after injury. regeneration is often compromised in the case of large lesions, and the speed of axon reconnection to their target is critical for successful functional recovery. We show that HDAC2 interacts with the transcription factor Sox[10] and recruits histone H3 lysine 9 (H3K9) HDMs to form a multifunctional protein complex that de-represses the Sox[10] target genes Oct[6] and Krox[20] to allow their subsequent activation at different time points of the regeneration process after lesion. Inactivating this mechanism results in earlier conversion into repair SCs after lesion and faster regeneration, but impairs remyelination
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
