The contribution of innate immune cells to regeneration of the zebrafish olfactory epithelium
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Date
2023
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Thesis (M.S.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2023.
Abstract
Tissue injury is immediately followed by a strictly coordinated immune response, which is necessary to restore the functional and structural integrity of the tissue. The regulation of the immune response is closely linked to the quality and extent of the regeneration process. Higher vertebrates exhibit a limited ability to accomplish complete regeneration of neuronal tissues. The peripheral olfactory epithelium (OE) on the other hand, undergoes a lifelong continuous turnover of sensory neurons. Regenerating organisms like the zebrafish, have even a higher capacity to achieve a rapid and full recovery of both central and peripheral nervous system tissue. This study aims to understand the relationship between innate immune cells and the regenerative events in the adult zebrafish OE by analyzing neutrophil and macrophage contributions to OSN neurogenesis following experimental injury. Qualitative analysis and quantitative assays established the baseline occupancy of neutrophils and macrophages in the intact tissue as well as their level of recruitment in response to injury. Using a cell type-specific depletion approach, temporal systemic elimination of neutrophils and macrophages was applied via VMO-knockdown and clodronate liposome administration, respectively. The selective contribution of neutrophils and macrophages to zebrafish olfactory sensory neurogenesis and regeneration were examined at the structural level. Systemic depletion of neutrophils resulted in a sharp decrease in the proliferative activity in the degenerated tissue and severely impaired the neurogenic process. Altogether, the results indicate that neutrophils may be regulating injury-induced repair neurogenesis and are necessary to achieve full regeneration of the OE. In contrast, neutrophils had no significant functional influence on the physiological turnover of the OE via maintenance neurogenesis events. Macrophages on the other hand, did not exhibit notable recruitment or showed any functional contribution to OSN neurogenesis.