Radial glia phagocytose axonal debris from degenerating over-extending axons in the developing olfactory bulb

Abstract

Axon targeting during the development of the olfactory system is not always accurate and numerous axons over-extend past the target layer into the deeper layers of the olfactory bulb. To date, the fate of the mis-targeted axons has not been determined. We hypothesised that following over-extension, the axons degenerate, and that cells within the deeper layers of the olfactory bulb phagocytose the axonal debris. We utilised a line of transgenic mice that expresses ZsGreen fluorescent protein in primary olfactory axons. We found that over-extending axons closely followed the filaments of radial glia present in the olfactory bulb during embryonic development. Following over-extension into deeper layers of the olfactory bulb, axons degenerated and radial glia responded by phagocytosing the resulting debris. We used in vitro analysis to confirm that the radial glia had phagocytosed debris from olfactory axons. We also investigated if the fate of over-extending axons was altered when the development of the olfactory bulb was perturbed. In mice that lacked Sox10, a transcription factor essential for normal olfactory bulb development, we observed a disruption to the morphology and positioning of radial glia and an accumulation of olfactory axon debris within the bulb. Our results demonstrate that during early development of the olfactory system, radial glia play an important role in removing over-extended axons from the deeper layers of the olfactory bulb.