Olfactory ensheathing cells: how different subpopulations regulate axon guidance

The glia of the olfactory system, olfactory ensheathing cells (OECs) are intimately associated with the axons of primary olfactory neurons that extend from the olfactory epithelium to their targets within the olfactory bulb. However, OECs are not a uniform population but instead there are different subpopulations each with a different molecular profile and proposed role in vivo. We have used OEC-axon assays and determined that OECs play an active role in modulating the growth of pioneer olfactory axons. The motility of OECs was mediated by GDNF, which stimulated cell migration and increased the apparent motility of the axons whereas loss of OECs via laser ablation of the cells inhibited olfactory axon outgrowth. These results demonstrate that the migration of OECs strongly regulates the motility of axons and that stimulation of OEC motility enhances axon extension and growth cone activity. We then determined that axons respond differently to OECs derived from the peripheral region of the olfactory nerve or from the olfactory bulb. We purified OECs from anatomically distinct regions of the olfactory bulb and used cell behaviour assays to reveal that OECs from the olfactory bulb are a functionally heterogeneous population with distinct differences which are consistent with their proposed roles in vivo. We found that the heterogeneity is regulated by motile lamellipodial waves along the shaft of the OECs and that inhibition of lamellipodial wave activity via Mek1 abolishes the ability of the cells to distinguish between each other. These results demonstrate that OECs from the olfactory bulb are a heterogeneous population that use lamellipodial waves to regulate cell-cell recognition.