Olfactory neurogenesis following acute injury

Abstract

For most of the last century, it was believed that neurogenesis is limited to embryonic development and does not occur in the adult nervous system. However, it is now an established fact that neurogenesis also occurs in the post-embryonic central and peripheral nervous system. Yet, adult neurogenesis is a limited process in mammals but more and widespread in lower vertebrates, such as teleost fish and amphibia. The olfactory sensory tissue is an attractive model to study neurogenesis due to its high regenerative capacity in lower and higher vertebrates. Olfactory sensory neurons undergo constant turnover and are replaced by adult-born cells. In addition to ongoing neurogenesis, which maintains the integrity of the tissue, the olfactory epithelium is also capable of mounting strong regenerative responses to acute injury. The differences and commonalities of the mechanisms that mediate these two different modes of neurogenesis are not well understood. Here, studies are described to functionally investigate the response of the olfactory epithelium to acute injury in zebrafish to understand the type, the location, and the properties of stem cells and signaling pathways that are involved in damage-induced neurogenesis. Tissue-wide degeneration of the olfactory epithelium was induced in combination with analysis of cell type-specific and proliferation markers to characterize the subpopulations of cells that respond to the injury and to investigate which molecular signaling pathways are activated. Neurogenesis in the unperturbed tissue is restricted to two distinct regions of proliferative activity, which are located on either end of the sensory tissue. The tissue response to chemical insult is rapid and within 12 h following treatment a significant increase in the number of proliferating cells can be detected. Different from the restricted pattern of maintenance neurogenesis, proliferative activity is distributed throughout the sensory tissue, suggesting that a distinct stem cell population located throughout the basal epithelium is recruited upon injury. Changes in gene expression following induced de- and regeneration was analyzed by transcriptome profiling to describe the molecular responses at different time points following damage.