DESCRIPTION: The main objective of this project is to elucidate the mechanisms underlying axon guidance in the olfactory system, using rodent models. Most mammalian species, including humans, have the ability to distinguish thousands of different odors. This ability is encoded in the organized connections made between olfactory sensory neurons in the nasal cavity and CNS neurons in the olfactory bulb. Axons from sensory neurons distributed widely in the nasal cavity converge onto a small number of targets called glomeruli that have fixed positions in the olfactory bulb. Conversely, axons from neighboring sensory neurons diverge to broadly defined zones in the olfactory bulb. This proposal focuses on the cells and extracellular matrix proteins that occupy axon pathways and the olfactory nerve layer that surrounds the olfactory bulb. The main cell type present in these regions is a special type of glial cell (ensheathing cell) that is unique to the olfactory system. It is hypothesized that ensheathing cells are molecularly heterogeneous and therefore present a differential environment to olfactory axons as they extend into the nerve layer of the olfactory bulb. Specific subpopulations of ensheathing cells have been shown to simultaneously present a permissive and non-permissive environment to unique subsets of olfactory axons. We propose to construct a map of the permissive and non-permissive regions of the nerve layer, defining the expression of guidance cues and the axons that they regulate. We will perturb interactions between axons and guidance cues in the nerve layer in vivo and in slice cultures of embryonic olfactory tissue in order to demonstrate functional activity in an intact system. We will also analyze development of ensheathing cells, in particular, the regulation of migration of precursor cells from the olfactory epithelium to the nerve layer of the olfactory bulb. These studies are intended to broaden our knowledge of mechanisms used to organize connections in the mammalian nervous system.