Development of the primary olfactory pathway

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DESCRIPTION (provided by applicant): The long term aim of this project is to identify axon guidance molecules involved in establishing the complex topography of the primary olfactory pathway. We previously identified some critical time points in development where axon behavior indicates that guidance molecules are acting. Olfactory sensory neuron (OSN) axons grow from the olfactory placode to the telencephalic vesicle in early embryonic development. Axons penetrate the telencephalon, forming a presumptive olfactory nerve layer (pONL). A subset of axons grow to the ventricular surface, which by way of stimulating cell cycle kinetics, the formation of olfactory bulb (OB) is induced. The majority of axons remain restricted to the pONL for up to 4 days, presumably sorting out into like subsets. After 4 days, some axons grow deeper into the OB, initiating glomerular formation. What are the cue(s) that are present in the OB that prevent axon in growth prior to glomerular formation? What cues are present in the ONL that prevent dendritic outgrowth amongst axons? Do pioneer axons exist that initiate individual glomeruli? Do pioneer axons or groups of axons use cues in the developing OB to position themselves in the appropriate position prior to glomerular induction? One way to answer these key questions is to examine the distributions of candidate guidance molecules within the developing pathway. We hypothesize that the stalling of axons within the pONL may be due to inhibitory guidance molecules within the developing OB. One source of such inhibitory cues may be components of the extra cellular matrix (ECM). We have examined the expression patterns of four ECM molecules, tenascin, laminin, perlecan, and chondroitin sulfate proteoglycans (CSPGs). Of these, members of the tenascin family appear particularly good candidates for the inhibitory cues that regulate axon in growth and glomerular formation. The specific aims of the current application are to: 1) identify members of the tenascin family that are expressed in the developing OB during the period of glomerular formation; and 2) to functionally test the ability of theses molecules to inhibit OSN neurite outgrowth in vitro. These studies will greatly enhance our knowledge of how axons establish connections in the olfactory system and may have implications for diseases such as Kallman's syndrome.