The extracellular matrix modulates olfactory neurite outgrowth on ensheathing cells

Primary olfactory axons grow along a stereotypical pathway from the nasal c avity 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 ol factory ensheathing cells, which provide a substrate conducive for axon gro wth 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 enshe athing 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 an d migration of olfactory ensheathing cells and hence did not promote olfact ory neurite outgrowth. In vitro olfactory axons grew preferentially on the surface of olfactory ensheathing cells rather than the underlying extracell ular matrix. We propose that olfactory ensheathing cells secrete laminin an d HSPGs, which together with other cofactors, stimulate these cells to migr ate 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 olfa ctory axons during development.