Axon Regeneration-Suppressing Genes Identified

A new study led by researchers at Yale School of Medicine has identified 40 genes actively involved in suppression of axon regeneration in central nervous system cells. By editing out one of those genes, they were able to restore axons in ocular nerves of mice damaged by glaucoma. Their findings were published in Cell Reports.

"This opens a new chapter in regeneration research," said senior author Stephen Strittmatter. Over the past several decades, Strittmatter and other scientists have found a handful of genes involved in suppressing regeneration of central nervous system cells. But the advent of RNAs to silence gene expression and new gene editing technologies capable of removing single genes and gauging their functional impact has allowed researchers to greatly expand their search for other culprits.

Among the 400 candidate genes the team had previously identified in cultures of cortical neurons, they were able to show that one in 10 of those genes had direct in vivo impact on axon regeneration in central nervous system cells in mice. One of the 40 genes edited out encodes for an immune system regulator known as interleukin-22. Elimination of this immune mediator altered the expression of many neuronal regeneration genes and greatly increased axon regeneration in mouse models of glaucoma, they found.

Future research will explore how modifying or blocking those 40 genes might affect the repair of neurons damaged by stroke and traumatic brain and spinal cord injuries, Strittmatter said.