Cellular, Molecular and Epigenetic Control of Axon Regeneration.
Permanent disabilities following central nervous system (CNS) injuries result from the failure of injured axons to regenerate and re-build functional connections. The poor regenerative capacity of mature CNS neurons remains a major problem in neurobiology and an unmet medical need. In contrast, axon regeneration and partial functional recovery do occur in injured peripheral nerves, providing an opportunity to identify molecular mechanisms that control the axon regeneration program.
We are using sensory neurons with cell body in dorsal root ganglia (DRG), one of the most useful mammalian models to study axon regeneration. Sensory neurons have a unique pseudo-unipolar morphology with a single axon which bifurcates within the ganglion; one axon proceeds centrally along the dorsal root into the spinal cord and the other proceeds along peripheral nerves. Importantly, the peripheral axon has a much greater regenerative capacity than the central axon.
The primary goal in the Cavalli lab is to reveal the principles and mechanisms by which injured sensory neurons re-activate a pro-regenerative program following peripheral axon injury and identify potential targets for future treatment of CNS injuries and severe PNS injuries. Indeed, functional recovery in the peripheral nervous system is often incomplete, especially after complete nerve transection or when axons need to re-grow long distances to reach their targets.
We use biochemical, molecular, cell biological, imaging, behavioral, genetic and epigenetic approaches in the mouse model system to elucidate the mechanisms controlling axon regeneration. We also use human tissue to determine if our findings in the mouse model system are relevant to the physiology of human neurons.
1. Epigenetic and transcriptional regulation of axon regeneration, click here.
2. Neuronal extrinsic contribution to nerve repair, click here.
3. Strategies to enhance axon regeneration in the injured central nervous system, click here
4. Role of the microtubule cytoskeleton in axon regeneration, click here.
COLLABORATORS at Washington University in St Louis:
Ram Dixit, Dept. of Biology
Rob Gereau, Dept. of Anesthesiology
Vitaly Klyachko, Dept. of Cell Biology and Physiology
Mayssa Mokalled, Dept. of Developmental Biology
Clay Semenkovich, Division of Endocrinology, Metabolism & Lipid Research