Presentation Details
| Zona pellucida like domain containing 2 mediates stimulation-dependent neurogenesis of specific olfactory sensory neuron subtypes in mice Karlin Rufenacht, Alexa Asson, Alyssa Granley, Kawsar Hossain, Amanda Stenzel, Madeline Smith, Stephen Santoro. Department of Pediatrics, Section of Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA |
Abstract
Neurogenesis occurs throughout life in the mammalian olfactory epithelium. In mice, each olfactory sensory neuron precursor selects for expression a single olfactory receptor gene, out of ~1200 possibilities, which determines the mature neuron’s subtype. We have found that odor stimulation can accelerate birthrates of specific neuron subtypes, which challenges the established model that olfactory neurogenesis is stochastic with respect to subtype. To explain these findings, we hypothesize that upon stimulation, neurons of some subtypes can signal to progenitors with predisposed subtype fates to selectively promote the birth of neurons of the same subtypes. In support of this, scRNA-seq analyses identified a few genes that are selectively expressed by subtypes whose birthrates are accelerated by stimulation, including Zona pellucida like domain containing 2 (Zpld2), which is predicted to encode an extracellular membrane protein with unknown function that is closely homologous to a protein known to bind complement components. To test whether Zpld2 plays a role in stimulation-dependent neurogenesis, we generated a Zpld2-null mouse. Using scRNA-seq, we found preliminary evidence that Zpld2-expressing neuron subtypes undergo stimulation-dependent neurogenesis and that this phenomenon is attenuated in Zpld2-null mice. These findings have been validated using EdU-birthdating combined with both RNA-FISH and snRNA-seq. Additionally, RNA-seq based analyses revealed a down-regulation of genes involved in neurogenesis and an up-regulation of genes involved in complement activation in Zpld2-null epithelia. These findings suggest a model in which, upon odor stimulation, neurons that express Zpld2 signal to progenitors, possibly via complement components, to promote the neurogenesis of specific neuron subtypes.
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