ROLE OF GALECTIN-1 IN THE DEVELOPING MOUSE OLFACTORY SYSTEM

Primary sensory olfactory neurons reside in a neuroepithelium lining t he nasal cavity and project topographically onto the surface of the ol factory bulb, a rostral extension of the telencephalon. Galectin-1, a bivalent galactose-binding vertebrate lectin, is expressed in the deve loping rodent olfactory system. In the present study, the mouse olfact ory neuron cell line 4.4.2 was used to examine the role of galectin-1 in neurite outgrowth in vitro. Recombinant galectin-1 has neurite outg rowth-promoting activity when used as a substrate for 4.4.2 cells. Whe n either galectin-1 or lactose was added to the culture media, the neu rite outgrowth-promoting activity was abolished. These results demonst rate that galectin-1 can modulate neurite growth in vitro. The in vivo role of galectin-1 was investigated by examining the topographical or ganization of the olfactory pathway in mice carrying a null mutation f or galectin-1. Using Dolichos biflorus agglutinin as a convenient hist ochemical marker of a subpopulation of primary sensory olfactory neuro ns which project topographically to the dorsomedial olfactory bulb, we show an aberrant topography of olfactory axons in the null mutants. A subset of primary sensory olfactory axons failed to project to their correct target sites in the caudal olfactory bulb. These data indicate that galectin-1 is involved in the growth and/or guidance of primary sensory olfactory axons between the nasal cavity and the olfactory bul b. This is the first demonstration that a lectin has neurite outgrowth -promoting activity and plays a role in neuronal pathfinding in the ma mmalian nervous system. (C) 1996 Academic Press, Inc.