| Summary: | 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. === Science, Faculty of === Zoology, Department of === Graduate
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