Spinal cord injury and axon regeneration; Neuronal development and migration
A major focus in the lab is to determine molecules that facilitate axonal regeneration after spinal cord injury. To date we have studied olfactory ensheathing cells (OECs) that are unique glia associated with the only adult neurons that are generated throughout life and project their axons from the PNS (nose) into the CNS (olfactory bulb). Dr. Phelps and her students, in collaboration with the Edgerton Lab, found that the transplantation of OEC above and below a complete spinal cord transection promotes axon regeneration and results in electrophysiological, anatomical, and behavioral changes in hindlimb function. Such findings suggest that OEC promote regeneration of mature axons and the reorganization of spinal circuitry, both of which contribute to sensorimotor function. Her laboratory also developed several culture models and found that OECs facilitate axon regeneration on a myelin substrate and that the brain-derived neurotrophic factor secreted by OEC is one mechanism by which these cells promote axon outgrowth. More recently we learned that OECs promote neurite outgrowth by direct cell-to-cell actions. Developmental studies in the lab focus on neuronal migration in the dorsal horn of the reeler spinal cord. Reelin, the protein absent in naturally occurring reeler mutants, is a large extracellular matrix molecule that binds to lipoprotein receptors (Vldl and Apoer2). Reelin signaling causes tyrosine phosphorylation of an intracellular adaptor protein Disabled1, which then initiates a cascade of events that lead to correct neuronal positioning. We found that the loss of Reelin-signaling causes hypersensitivity to thermal nociception and insensitivity to mechanical stimulation. Current experiments focus on dissecting the cellular defects that underlie this unusual combination of nociceptive defects.
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