Purinergic Signaling Regulates Cell Proliferation of Olfactory Epithelium Progenitors

Abstract

In the olfactory epithelium (OE) continuous neurogenesis is maintained throughout life. The OE is in direct contact with the external environment, and its cells are constantly exposed to pathogens and noxious substances. To maintain a functional sense of smell the OE has evolved the ability to permanently replenish olfactory receptor neurons and sustentacular cells lost during natural turnover. A cell population residing in the most basal part of the OE, the so-called basal cells (BCs), keep up this highly regulated genesis of new cells. The population of BCs is thought to include both the stem cells of the OE and various progenitor cells. In recent years a number of regulatory factors that positively and/or negatively regulate the proliferation within the OE have been identified, but a thorough comprehension of the complex interplay of these regulatory factors and the role of the different epithelial cell types is still illusive. Combining labeling techniques, immunohistochemistry, electron microscopy, functional calcium imaging, and a bromo-2'-deoxyuridine incorporation assay, we show for the first time that purinergic receptors are expressed in BCs of the OE of larval Xenopus laevis and that nucleotide-induced Ca(2+) signaling in these cells is involved in the regulation of the cell turnover in the OE. Our data contribute to a better understanding of the regulation of the cell turnover in the OE in particular and also of how the proliferation of neuronal progenitor cells is regulated in general. STEM CELLS 2009;27:2022-2031