Search
Presentation Details
| Poster #114 The role of the complement system in regulating the stimulation-dependent neurogenesis of specific olfactory sensory neuron subtypes in mice |
| Alexa J. Asson, Madeline Smith, Karlin E. Rufenacht, Kawsar Hossain, Rebecca O. Rourke, Stephen W. Santoro Department of Pediatrics, Section of Developmental Biology, University of Colorado | Anschutz Medical Campus , Aurora, CO, United States |
Of the roughly 1200 olfactory sensory neuron (OSN) subtypes in the mouse olfactory epithelium (as defined by odorant receptor identity), a fraction has been found to undergo accelerated birth rates in the presence of odor stimulation compared to the absence. These findings challenge the established model that OSN neurogenesis is entirely stochastic with respect to subtype. We hypothesize that mature OSNs of this fraction of subtypes possess the unique ability to signal to proximate neuronal progenitors and thereby promote their proliferation in the presence of specific olfactory stimuli. To test this, scRNA-seq was used to compare the transcriptomes of OSN subtypes known to undergo stimulation dependent neurogenesis to those of random subtypes, revealing Cd55, a gene encoding a central inhibitor of the complement system, as one of a small number of genes selectively enriched in stimulation-dependent subtypes. Based on these findings, we hypothesized that CD55 plays a role in regulating stimulation-dependent OSN neurogenesis. To test this, we generated a mouse in which Cd55 is knocked out specifically in neurons. Utilizing scRNA-seq and a combination of EdU-birthdating and RNA fluorescent in situ hybridization, we have found preliminary evidence that the birth rates of Cd55-expressing OSN subtypes are accelerated by stimulation, that the effects of odor stimulation are attenuated in Cd55-knockout mice compared to controls, and that the overall rate of OSN neurogenesis is increased in Cd55-knockout mice. Taken together, our findings support a model in which the selective expression of CD55 by OSNs of a fraction of subtypes inhibits the activation of complement in their proximity and thereby selectively reduces the neurogenesis rates of specific subtypes in the absence of odor stimulation. |