Dynamic spatiotemporal expression patterns of neurocan and phosphacan indicate diverse roles in the developing and adult mouse olfactory system

The chondroitin sulfate proteoglycans neurocan and phosphacan are believed to modulate neurite outgrowth by binding to cell adhesion molecules, tenasc in, and the differentiation factors heparin-binding growth-associated molec ule and amphoterin. To assess the role of these chondroitin sulfate proteog lycans in the olfactory system, we describe here their expression patterns during both embryonic and postnatal development in the mouse. Immunoreactiv ity for neurocan was first detected in primary olfactory neurons at embryon ic day 11.5 (E11.5). Neurocan was expressed by primary olfactory axons as t hey extended toward the rostral pole of the telencephalon as well as by the ir arbors in glomeruli after they contacted the olfactory bulb. The role of neurocan was examined by growing olfactory neurons on an extracellular mat rix substrate containing neurocan or on extracellular matrix in the presenc e of soluble neurocan. In both cases, neurocan strongly promoted neurite ou tgrowth. These results suggest that neurocan supports the growth of primary olfactory axons through the extracellular matrix as they project to the ol factory bulb during development. Phosphacan, unlike neurocan, was present w ithin the mesenchyme surrounding the E11.5 and E12.5 nasal cavity. This exp ression decreased at E13.5, concomitant with a transient appearance of phos phacan in nerve fascicles. Within the embryonic olfactory bulb, phosphacan was localised to the external and internal plexiform layers. However, durin g early postnatal development phosphacan was concentrated in the glomerular layer. These results suggest that phosphacan may play a role in delineatin g the pathway of growing olfactory axons as well as defining the laminar or ganization of the bulb. Together, the spatiotemporal expression patterns of neurocan and phosphacan indicate that these chondroitin sulfate proteoglyc ans have diverse in situ roles, which are dependent on context-specific int eractions with extracellular and cell adhesion molecules within the develop ing olfactory nerve pathway. (C) 2000 Wiley-Liss, Inc.