| Abstract No.: | B-A2019 |
| Country: | Canada |
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| Title: | SEMAPHORIN 5B IS A NOVEL INHIBITORY COMPONENT OF THE CORTICOFUGAL PROJECTION |
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| Authors/Affiliations: | 1 Robyn Lett*; 1 Wenyan Wang; 1 Timothy O'Connor;
1 University of British Columbia, Vancouver, BC, Canada
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| Content: | Neuronal connectivity is generated by the precise guidance of neuronal growth cones in response to the spatiotemporal distribution of molecular guidance cues in the developing embryo. Connections between cortex and subcortical targets such as the thalamus are among the longest and most complex projections of the mammalian forebrain, requiring many intermediate targets and guidance decisions.
Objective:
The class 5 semaphorin, Sema5B, is expressed in germinal zones, important histogenic boundaries and regions of the subcortex flanking the internal capsule during descending cortical axon guidance. The purpose of this study was to elucidate the role of Sema5B in the formation of this fiber tract.
Methods and Results:
Axons from cortical explants cultured in vitro with Sema5B-expressing cells exhibited characteristic avoidance behaviors suggesting Sema5B functions as a repulsive guidance cue. To further test this, Sema5B expressing cells were transplanted onto organotypic slices along the presumptive internal capsule. Ectopic Sema5B was sufficient to cause cortical axons to avoid their normal trajectory, resulting in either stalling at the boundary of Sema5B or turning into inappropriate areas of the cortex. When testing whether the same would be true of the reciprocal thalamocortical pathway, we found quite unexpectedly that thalamocortical axons were not inhibited either in vitro or in slice culture by ectopic Sema5B. We then knocked down Sema5B expression from the ventricular zone at the vicinity of the corticostriatal angle by ex vivo electroporation of shRNA-iresGFP vectors at E13.5 and found that cortical fibers aberrantly navigated into GFP+ (and thus Sema5B-) ventricular zones.
Conclusion: We therefore propose that Sema5B is not only sufficient to inhibit the corticofugal projection but is also necessary to ensure cortical axons are excluded from germinal zones and inappropriate subcortical regions during forebrain tract development.
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