Presentation Details
| Zona pellucida like domain containing 2 is involved in the stimulation-dependent neurogenesis of specific olfactory sensory neuron subtypes in mice Karlin E Rufenacht, 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 persists throughout life in the mammalian olfactory epithelium. In mice, each differentiating olfactory sensory neuron precursor selects to express, out of ~1200 possibilities, a single olfactory receptor gene, which determines the mature neuron’s subtype. Our lab has found that odor stimulation can accelerate the birthrates of specific neuron subtypes. These findings challenge the established model that neurogenesis within the olfactory epithelium is stochastic with respect to subtype. To explain these findings, we hypothesize that upon stimulation, neurons of some subtypes can signal to progenitors to promote the birth of neurons of the same subtype. To test this, we used scRNA-seq to identify genes enriched in neuron subtypes whose birthrates are accelerated by stimulation. Zona pellucida like domain containing 2 (Zpld2), a gene with no known function that is expressed only in the olfactory epithelium and predicted to be a member of the TGF-β receptor type III protein family, was the gene found most enriched. These findings are consistent with the hypothesis that Zpld2 is a component of a signaling pathway that mediates stimulation-dependent neurogenesis. To test this, we generated and analyzed the phenotypes of a Zpld2-null mouse. Using a combination of EdU-birth dating and RNA fluorescent in situ hybridization, we have found evidence that the effect of olfactory deprivation on the birthrates of neuron subtypes that undergo stimulation-dependent neurogenesis is reduced in Zpld2-null mice. Additionally, gene ontology analyses of RNA-seq data from Zpld2-null epithelia reveal that genes involved in the regulation of neurogenesis and TGF-β signaling are down-regulated in Zpld2-nulls. These findings suggest that Zpld2 mediates stimulation-dependent signaling to promote neurogenesis.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.