Two phases of replacement replenish the olfactory ensheathing cell population after injury in postnatal mice

Abstract

Olfactory ensheathing cells (OECs) support the regeneration of olfactory sensory neurons throughout life, however it remains unclear how OECs respond to a major injury. We have examined the proliferation and migration of OECs following unilateral bulbectomy in postnatal mice. S100߭DsRed and OMP-ZsGreen transgenic mice were used to visualise OECs and olfactory neurons, respectively, and we used the thymidine analogue ethynyl deoxyuridine (EdU) to identify cells that were proliferating at the time of administration. Following unilateral bulbectomy, there was an initial phase of OEC proliferation throughout the olfactory pathway with a peak of proliferation occurring 2-7 days after the injury. A second phase of proliferation also occurred in which precursors localised within the olfactory mucosa divided to replenish the OEC population. We then tracked the positions of OECs that had proliferated and found that there was a progressive increase in OECs in the cavity for at least 12-16 days after injury which could not be accounted for solely by local proliferation of OECs within the cavity. These results suggest that OECs migrated from the peripheral olfactory nerve to populate the mass of cells that filled cavity left by bulbectomy. Our results demonstrate that following injury to the olfactory nervous system, the OEC population is replenished by migration of cells that arise from both local proliferation of OECs throughout the olfactory nerve pathway as well as from precursor cells in the olfactory mucosa.