Purinergic signalling selectively modulates maintenance but not repair neurogenesis in the zebrafish olfactory epithelium

FEBS J. 2020 Jul;287(13):2699-2722. doi: 10.1111/febs.15170. Epub 2019 Dec 29.

Abstract

Olfactory sensory neurons (OSNs) of the vertebrate olfactory epithelium (OE) undergo continuous turnover but also regenerate efficiently when the OE is acutely damaged by traumatic injury. Two distinct pools of neuronal stem/progenitor cells, the globose (GBCs), and horizontal basal cells (HBCs) have been shown to selectively contribute to intrinsic OSN turnover and damage-induced OE regeneration, respectively. For both types of progenitors, their rate of cell divisions and OSN production must match the actual loss of cells to maintain or to re-establish sensory function. However, signals that communicate between neurons or glia cells of the OE and resident neurogenic progenitors remain largely elusive. Here, we investigate the effect of purinergic signaling on cell proliferation and OSN neurogenesis in the zebrafish OE. Purine stimulation elicits transient Ca2+ signals in OSNs and distinct non-neuronal cell populations, which are located exclusively in the basal OE and stain positive for the neuronal stem cell marker Sox2. The more apical population of Sox2-positive cells comprises evenly distributed glia-like sustentacular cells (SCs) and spatially restricted GBC-like cells, whereas the more basal population expresses the HBC markers keratin 5 and tumor protein 63 and lines the entire sensory OE. Importantly, exogenous purine stimulation promotes P2 receptor-dependent mitotic activity and OSN generation from sites where GBCs are located but not from HBCs. We hypothesize that purine compounds released from dying OSNs modulate GBC progenitor cell cycling in a dose-dependent manner that is proportional to the number of dying OSNs and, thereby, ensures a constant pool of sensory neurons over time.

Keywords: adult neurogenesis; olfactory epithelium; purine signaling; stem cells; zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Cell Differentiation
  • Cell Proliferation
  • Neural Stem Cells / drug effects*
  • Neural Stem Cells / metabolism
  • Neurogenesis*
  • Olfactory Mucosa / drug effects*
  • Olfactory Mucosa / metabolism
  • Olfactory Receptor Neurons / drug effects*
  • Olfactory Receptor Neurons / metabolism
  • Purines / pharmacology*
  • Receptors, Purinergic / metabolism*
  • SOXB1 Transcription Factors / metabolism
  • Signal Transduction
  • Zebrafish

Substances

  • Purines
  • Receptors, Purinergic
  • SOXB1 Transcription Factors
  • Calcium