Inhibition of focal adhesion kinase limits axon growth from olfactory sensory neurons following injury
Abstract
Regeneration of olfactory sensory neurons (OSNs) in the adult olfactory epithelium (OE), which is a cellular layer that lines the sinuses, maintains the sense of smell. New OSNs extend their axons from the OE to the olfactory bulb, the nasal processing center of the brain, via the lamina propria layer. Adhesion inhibition restricts axon growth by blocking cell-substrate interactions like integrin, a receptor for cell signals, and extracellular matrix molecules. Integrin signals through Focal Adhesion Kinase (FAK). FAK uses integrin to determine how cells layer, move, duplicate, and change. Using FAK to see how it affects axon growth, we traced axons using the flourecent protein,Tdtomato (Tdt), in the lamina propria to see how far axons were extending using Mash1Cre-Tdtomato (Tdt) mice. These mice are engineered to have the Tdt + protein expressed in Mash1+ neuronal progenitor (stem) cells. After causing nasal injury, we measured the area of GAP43+ axons (GAP43 is a protein that show major neuron growth) that came from newly generated immature OSNs that extended into the lamina propria. Mash1Cre-Tdt mice were then treated with methimazole to deplete OSNs and initiate neuroregeneration. At 3-5 days after giving methimazole, 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 also showing that FAK14 limits axon growth. Olfactory ensheathing cells (OECs) help facilitate axon growth. To examine whether OECs also contribute to the effect of FAK inhibition, we selectively removed FAK in OECs of GFAPCre-FAKfl/fl mice and removed the olfactory bulb to deplete OSNs. At 5 days post-bulbectomy removal, GFAPCre-FAKfl/fl mice had less GAP43+ area in the lamina propria than FAKfl/fl controls. Together, this data suggests that FAK promotes axon growth and extension, possibly through OECs. Which means, activation of FAK signaling may facilitate recovery of the sense of smell following injury, virial infection or aging.
Start Time
15-4-2026 1:30 PM
End Time
15-4-2026 4:30 PM
Room Number
Culp Ballroom 316
Poster Number
31
Presentation Type
Poster
Presentation Subtype
Posters - Competitive
Presentation Category
Science, Technology, and Engineering
Student Type
Undergraduate Student
Faculty Mentor
Cuihong Jia
Inhibition of focal adhesion kinase limits axon growth from olfactory sensory neurons following injury
Culp Ballroom 316
Regeneration of olfactory sensory neurons (OSNs) in the adult olfactory epithelium (OE), which is a cellular layer that lines the sinuses, maintains the sense of smell. New OSNs extend their axons from the OE to the olfactory bulb, the nasal processing center of the brain, via the lamina propria layer. Adhesion inhibition restricts axon growth by blocking cell-substrate interactions like integrin, a receptor for cell signals, and extracellular matrix molecules. Integrin signals through Focal Adhesion Kinase (FAK). FAK uses integrin to determine how cells layer, move, duplicate, and change. Using FAK to see how it affects axon growth, we traced axons using the flourecent protein,Tdtomato (Tdt), in the lamina propria to see how far axons were extending using Mash1Cre-Tdtomato (Tdt) mice. These mice are engineered to have the Tdt + protein expressed in Mash1+ neuronal progenitor (stem) cells. After causing nasal injury, we measured the area of GAP43+ axons (GAP43 is a protein that show major neuron growth) that came from newly generated immature OSNs that extended into the lamina propria. Mash1Cre-Tdt mice were then treated with methimazole to deplete OSNs and initiate neuroregeneration. At 3-5 days after giving methimazole, 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 also showing that FAK14 limits axon growth. Olfactory ensheathing cells (OECs) help facilitate axon growth. To examine whether OECs also contribute to the effect of FAK inhibition, we selectively removed FAK in OECs of GFAPCre-FAKfl/fl mice and removed the olfactory bulb to deplete OSNs. At 5 days post-bulbectomy removal, GFAPCre-FAKfl/fl mice had less GAP43+ area in the lamina propria than FAKfl/fl controls. Together, this data suggests that FAK promotes axon growth and extension, possibly through OECs. Which means, activation of FAK signaling may facilitate recovery of the sense of smell following injury, virial infection or aging.
