Nerve Regeneration Genes Discovered

Spinal cord injury (SCI) results in damage to the cells that transmit electrical signals (neurons) between the brain and the body. Different types of neurons in the central nervous system (CNS) respond differently to an injury. Most neurons die following an injury, while others survive but fail to regenerate axons. However, a small of number of neurons have a unique ability to survive and regenerate. It has long been thought that if researchers could decipher the molecular pathways that operate in these cells, it could provide important clues toward developing nerve regeneration strategies that promote survival and regeneration in all neurons after SCI and other CNS injury.

A special type of neuron found in the optic nerve, called intrinsically photo-sensitive retinal ganglion cells (ipRGCs), has been shown to be resilient to cell death and highly regenerative. However, results from previous studies have been variable and it remained unclear what caused these specific cells to survive and regenerate after injury. Recently, scientists at The Miami Project to Cure Paralysis used sophisticated techniques to sequence the genetic profiles of ipRGCs in specially bred, transgenic mice with the goal of identifying whether specific genes may be responsible for their unique abilities.

Dr. Kevin Park, Associate Professor, Department of Neurological Surgery and The Miami Project to Cure Paralysis, along with graduate student, Eric Bray, and colleagues found that two distinct genes, THBS1 and syndecan-1, are differentially expressed in ipRGCs and associate with their survival and axon regeneration. When the team eliminated THBS1 from the cells, axons failed to regenerate. Conversely, when the team caused the cells to produce more THBS1, regeneration was enhanced in the ipRGCs, as well as non-ipRGC neurons. In addition, Miami Project scientists showed that the other gene, syndecan-1, is closely associated with THBS1 and plays a role in axon regeneration. Their results were recently published in the journal Neuron.

“These findings raise interesting questions about manipulating these genes, and others that were revealed in the study, to promote regeneration in other types of neurons in the CNS, including those that control sensory and motor functions in the spinal cord,” said Dr. Park.

Dr. Park and his colleagues at The Miami Project who are studying nerve regeneration continue to investigate alternative strategies to improve axon regeneration, which may result in improved function for people living with SCI and other CNS injuries.