Methods: We generated a surgical model of partial sciatic nerve injury in mice to mechanistically study degeneration-induced collateral sprouting from spared fibers in the peripheral nervous system. Using next-generation sequencing and Ingenuity Pathway Analysis we described the sprouting-associated transcriptome of uninjured sensory neurons and compare it with the activated by regenerating neurons. In vitro approaches were used to functionally assessed sprouting genes candidates in the mechanisms of axonal growth.
Results: Using a novel animal model we provide the first description of the sprouting transcriptome observed in uninjured sensory neurons after nerve injury. This collateral sprouting-associated transcriptome differs from that seen in regenerating neurons, suggesting a molecular program distinct from axonal growth. We further demonstrate that genetic upregulation of novel sprouting associated genes activates a specific growth program in vitro, leading to increased neuronal branching.
Conclusions: These results contribute to our understanding of the molecular mechanisms associated with collateral sprouting in vivo. The data provided here will therefore be instrumental in developing therapeutic strategies aimed at promoting functional recovery after injury to the nervous system.
- Axonal regeneration
- Collateral sprouting
- Nerve injury
- Sciatic nerve
- Royal (Dick) School of Veterinary Studies - Group Leader
- Euan MacDonald Centre for Motor Neurone Disease Research
- Edinburgh Neuroscience
Person: Academic: Research Active , Academic: Research Active (Research Assistant)