Presentation Details
| AChemS Undergrad Finalist: Inhibition of focal adhesion kinase limits axon growth from olfactory sensory neurons following injury Morning Dove TJ Rose, Derek Cox, Diego Rodriguez-Gil, Cuihong Jia. Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA |
Abstract
Regeneration of olfactory sensory neurons (OSNs) in the adult olfactory epithelium (OE) maintains the sense of smell. New OSNs extend their axons from the OE to the olfactory bulb via the lamina propria. Adhesion inhibition restricts axon growth by blocking cell-substrate interaction, including integrin and extracellular matrix molecules. Integrin signals through FAK. To determine whether FAK affects axon growth, we fate-traced Tdtomato (Tdt)+ axons in the lamina propria in Mash1Cre-Tdtomato (Tdt) mice in which Tdt protein was expressed in Mash1+ neuronal progenitor cells. We measured GAP43+ axons that came from newly generated immature OSNs following injury and extended into the lamina propria. Mash1Cre-Tdt mice were treated with methimazole to deplete OSNs and initiate neuroregeneration. At 3-5 days, we treated mice with saline or FAK inhibitor, FAK14, intranasally. 24 h later, GAP43+ axons extended into the lamina propria. Compared to saline, FAK14 reduced GAP43+ area, suggesting that FAK14 limits axon growth and extension. FAK14 also appeared to reduce Tdt+ axons in the lamina propria. Olfactory ensheathing cells (OECs) facilitate axon growth. To examine whether OECs contribute to the effect of FAK inhibition, we selectively knocked out FAK in OECs of GFAPCre-FAKfl/fl mice and performed bulbectomy to deplete OSNs. At 5 days post-bulbectomy, GFAPCre-FAKfl/fl mice had less GAP43+ area in the lamina propria than FAKfl/fl controls. Together, these data suggest that FAK promotes axon growth and extension, possibly through OECs. Thus, activation of FAK signaling may facilitate recovery of the sense of smell following injury, virial infection or aging.
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