UBC Theses and Dissertations
Plexin expression in axotomized rubrospinal and facial motoneurons Spinelli, Egidio
Injuries to the central nervous system (CNS) are characterized by the inability of most axons to regenerate to their respective target tissues leading to permanent loss of sensory/motor function, while following peripheral nervous system (PNS) injuries, regeneration can occur. The failure of CNS nerve regeneration is partly attributed to the inhibitory nature of the CNS injury site. Apart from their roles in nervous system patterning during development, inhibitory guidance molecules present at the spinal cord injury site, such as semaphorins, have been suggested to contribute to the inhibitory nature of the CNS injury site. Secreted class 3 semaphorins bind to a receptor complex composed of neuropilins, the ligand binding subunit, and plexins, the signal transducing component. Although injured CNS and PNS neurons continue to express neuropilins, little is known about the expression patterns of plexins by axotomized neurons. This study analyzes class-A plexins and plexin-Bl expression in injured CNS (rubrospinal) and PNS (facial) neurons. Plexin mRNA and protein expression were analyzed over a period of 2 weeks in injured mouse rubrospinal and facial motoneurons after cervical spinal cord hemisection and facial nerve resection, respectively. In rubrospinal neurons, Plxn-Al mRNA and protein and Plxn-A4 mRNA expression did not differ between injured and uninjured neurons while Plxn-A2 mRNA expression increased in injured compared to uninjured rubrospinal neurons. Plxn-A3 mRNA was not detected in rubrospinal neurons. In facial motoneurons, Plxn-Al, -A3 and -A4 mRNA expression was higher in injured compared to uninjured motoneurons, although Plxn-Al protein expression did not change between injured and uninjured neurons. Plxn-A2 mRNA, on the other hand, decreased in injured facial motoneurons. Plxn-Bl mRNA expression was absent from both rubrospinal and facial neurons. Therefore, most class-A plexins continue to be expressed in both rubrospinal and facial motoneurons after injury, suggesting that these neuronal populations will remain responsive to semaphorins present at the injury site. This study provides a crucial step in understanding how injured neurons may respond to semaphorins and which components of the semaphorin response; either plexins, neuropilins or semaphorins, may be targeted to promote successful CNS nerve regeneration.
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