The extracellular matrix modulates olfactory neurite outgrowth on ensheathing cells

Primary olfactory axons grow along a stereotypical pathway from the nasal cavity to the olfactory bulb through an extracellular matrix rich in laminin and heparan sulfate proteoglycans (HSPGs) and bounded by the expression of chondroitin sulfate proteoglycans (CSPGs). This pathway is pioneered by olfactory ensheathing cells, which provide a substrate conducive for axon growth during early development. In the present study, we examined the effect of several extracellular matrix constituents on the spreading and migration, as well as the neurite outgrowth-promoting properties, of olfactory ensheathing cells. Laminin and Matrigel enhanced the spreading and migration of olfactory ensheathing cells and increased their neurite outgrowth-promoting activity. In contrast, HSPG and CSPG had little effect on the spreading and migration of olfactory ensheathing cells and hence did not promote olfactory neurite outgrowth. In vitro olfactory axons grew preferentially on the surface of olfactory ensheathing cells rather than the underlying extracellular matrix. We propose that olfactory ensheathing cells secrete laminin and HSPGs, which together with other cofactors, stimulate these cells to migrate and adopt a neurite outgrowth-promoting phenotype. Expression of CSPGs in the surrounding mesenchyme confines the growth of ensheathing cells, as well as the axons, which grow on the surface of these cells, to a specific pathway. Thus, the ECM indirectly modulates the growth and guidance of olfactory axons during development.