Title: Polycomb regulation of nerve injury.
Legend: These results show that an epigenetic complex, called polycomb repressive complex 2 (PRC2), is required for nerve regeneration after nerve injury. Using electron microscopy of nerve cross-sections, the lack of myelin (dark rings around axons) and loss of axons in the Eed-deficient sample is evident at 14 days after injury. Eed is a subunit of the PRC2 complex, and it is not required for myelination as shown for the 2 month (uninjured) sample. Another subunit of the PRC2 complex, Ezh2 is induced by injury in Schwann cells. (Data from Joseph Ma in the Svaren laboratory)
- Ma KH, Hung HA, Svaren J. (2016). Epigenomic Regulation of Schwann Cell Reprogramming in Peripheral Nerve Injury. Journal of Neuroscience. 31;36(35):9135-47. doi: 10.1523/JNEUROSCI.1370-16.2016.
- Ma KH, Hung HA, Srinivasan R, Xie H, Orkin SH, Svaren J. (2015). Regulation of Peripheral Nerve Myelin Maintenance by Gene Repression through Polycomb Repressive Complex 2. Journal of Neuroscience. 3;35(22):8640-52. doi: 10.1523/JNEUROSCI.2257-14.2015.
Significance Statement: Peripheral nerve regeneration after injury is dependent upon implementation of a novel genetic program in Schwann cells that supports axonal survival and regeneration. Although recent progress has identified transcriptional determinants of successful reprogramming of the Schwann cell transcriptome after nerve injury, our results have highlighted a novel epigenomic pathway in which reversal of the Polycomb pathway of repressive histone methylation is required for activation of a significant number of injury-induced genes.
About the Lab: The Svaren laboratory is focused on the transcriptional and epigenetic regulation of myelination. Myelin is a vital constituent of the nervous system that increases the speed of action potentials, and also provides trophic support for the long axons that project from neurons. Their studies are centered on the myelin-producing cells of the peripheral nervous system, called Schwann cells. The Svaren lab has focused on elucidating regulation of gene networks during Schwann cell development and response to injury. They have also recently found a novel role of the polycomb repressive complex 2, an epigenetic regulator, in controlling the regenerative responses of Schwann cells after peripheral nerve injury.