Purinergic signalling selectively modulates maintenance but not repair neurogenesis in the zebrafish olfactory epithelium.
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.
['Demirler|Mehmet Can|MC|', 'Sakizli|Uğurcan|U|', 'Bali|Burak|B|', 'Kocagöz|Yiğit|Y|', 'Eski|Sema Elif|SE|', 'Ergönen|Arda|A|', 'Alkiraz|Aysu Sevval|AS|', 'Bayramli|Xalid|X|', 'Hassenklöver|Thomas|T|', 'Manzini|Ivan|I|', 'Fuss|Stefan H|SH|0000-0002-3076-1121']
D000818:Animals D002118:Calcium D002454:Cell Differentiation D049109:Cell Proliferation D058953:Neural Stem Cells D055495:Neurogenesis D009831:Olfactory Mucosa D018034:Olfactory Receptor Neurons D011687:Purines D011983:Receptors, Purinergic D055748:SOXB1 Transcription Factors D015398:Signal Transduction D015027:Zebrafish
zebrafish olfactory epithelium stem cells adult neurogenesis purine signaling