The Initial Axon Outgrowth from the Olfactory Epithelium

Abstract

The olfactory system provides an outstanding model that allows for the understanding of the mechanisms that drive neurodevelopment and axon-glia interactions. This system is unique because new neurons are constantly generated from stem cells that line the basal layer of the olfactory epithelium and the new axons extend from the epithelium into central nervous system where they terminate. The glia of the olfactory system, the olfactory ensheathing cells (OECs), are thought to be essential for the regenerative capacity of the olfactory system. However the initial outgrowth of axons and the interactions with OECs during early development are poorly understood. To visualise olfactory axons in early development we used OMP-ZsGreen transgenic mice at the ages E10.25 to E13 (n=3 at each age). The bright fluorescence of the ZsGreen enabled us to view growth cone morphology and track the trajectory of the axons as they exited the basal layer of the olfactory epithelium and projected into the central nervous system. Using the ZsGreen axons, combined with a more sensitive immunohistochemistry protocol, we have identified that olfactory sensory neurons first arise at E10.25 and their axons penetrate the telencephalon at E11.0. At E10.75 we have also identified the presence of dendrites projecting from the olfactory neurons. OECs migrate ahead of the axons and establish the pathway through which the axons extend which can be seen from as early as E11. These results demonstrate that the establishment of the olfactory nerve pathway is dependent on the migration of OECs and that olfactory axons penetrate the olfactory bulb earlier than previously thought.