RETINOID SIGNALING DISTINGUISHES A SUBPOPULATION OF OLFACTORY RECEPTOR NEURONS IN THE DEVELOPING AND ADULT-MOUSE

We asked whether retinoic acid (RA) influences olfactory receptor neur ons (ORNs) in the developing and mature mouse olfactory epithelium (oe ). The distribution of retinoid receptors and binding proteins in the oe changes between embryonic days 11.5 and 13.5, the period when ORNs first differentiate and send axons into the nascent olfactory nerve. C oincident with this change, RA, which is produced in the frontonasal m esenchyme at these ages, begins to activate gene expression in a bilat erally symmetric subset of ORNs in the dorsolateral oe, as judged by t he expression of an RA-responsive transgene. Axons from these RA-activ ated ORNs are segregated in the olfactory nerve as it extends through the frontonasal mesenchyme toward the forebrain. In vitro, RA potentia tes ORN neurite growth on laminin, which, in the embryo, is found in a stripe of frontonasal mesenchyme directly associated with the olfacto ry nerve. RA does not modify growth on fibronectin, type IV collagen, or L1, which olfactory axons encounter in different regions of the ter ritory between the olfactory epithelium and the brain. The pattern of RA-mediated transcriptional activation and axon segregation persists i n early postnatal mice, and RA signaling can be recognized in a subset of adult ORNs in the dorsolateral oe. Thus, RA-mediated gene expressi on distinguishes a subpopulation of ORNs in a distinct region of the o e during the early development of the olfactory pathway, and may influ ence differentiation and axonal projections of ORNs in this region thr oughout life. J. Comp. Neurol. 394:445-461, 1998. (C) 1998 Wiley-Liss. Inc.