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The mechanisms regulating neural development are beginning to relinquish their secrets through molecular biological investigations of simple model systems. We use the peripheral olfactory system, consisting of the olfactory epithelium and the olfactory bulb (its CNS target) to model fundamental developmental processes (see summary diagram modified from Cajal, below). We take advantage of the system's remarkable capacity to recover after injury -- i.e., to reconstitute the olfactory epithelium and its constituent sensory neurons, and to reinnervate the olfactory bulb -- throughout life. Thus, one can use an adult lesion model to study the controlled generation of neurons and directed axon growth, with all of the experimental advantages attendant on using a lesion-regeneration paradigm. Furthermore, the olfactory system offers exquisite examples of both the generation of neuronal diversity and highly targeted axon growth, since the roughly 1000 different types of olfactory neurons that are generated (each type defined by the expression of only one gene from the large family of odorant receptor genes) each innervate only a pair from among the roughly 2000 glomeruli (small pockets of neuropil) that form the outer layer of the bulb. These and other findings indicate that the odorant receptor itself participates in some as yet unknown fashion in directing glomerular targeting, which process can be termed receptotopy as a consequence. We want to know how it is that the olfactory system retains the capacity to reconstitute its neuronal population and reinnervate the bulb and to use that knowledge to understand CNS development and to promote recovery after injury. Images (click on image for a detailed view)
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