Differential reaction of outgrowing olfactory neurites monitored in explant culture

Olfactory sensory neurons (OSNs) send their axons to distinct glomeruli in the olfactory bulb. On the way to their target, outgrowing axons are guided, fasciculated, and resorted before they extend in homotypic bundles to the glomerulus. The molecular mechanisms underlying these complex processes supposedly involve multiple intrinsic and extrinsic cues. Although the contribution of typical guidance molecules has been proposed, a detailed understanding of the olfactory wiring process remains elusive. By using in vitro cultures of the olfactory epithelium (OE) from gene-targeted mice, which allowed visualization of mature OSN and their axons, the impact of distinct molecular and cellular cues on defined OSN populations could be studied. The differentiating factor retinoic acid induced a heterogeneous response pattern of OMP expression and axon elongation. Cocultures with forebrain explants revealed that tissue from the presumptive olfactory bulb of embryonic stage E14 exhibited nonpermissive, repellent effects on outgrowing neurites, whereas precultured bulb tissue strongly attracted them, even from distantly located OE explants. A selective attraction of fibers from OSNs expressing defined odorant receptor types to distinct bulb explants was observed. These data indicate a differential reaction of OSNs to their target tissue.