The working hypothesis of this project is that the olfactory system, like other sensory systems, contains primary sensory cells with preferential sensitivities to distinct stimuli. Our previous experiments have defined several molecularly distinct olfactory primary neurons subsets in frog and rat and found common cell surface components between first and second order neurons in the frog. mAb 9-OE reacts with an olfactory specific carbohydrate group expressed by many olfactory cells in adult frog and also by vomeronasal neurons (VNO) in adult rat. On frog second order olfactory neurons 9-OE expression uniquely on the neural cell adhesion molecule. We propose to examine 9-OE expression during frog development to determine if it has the potential to be involved in the formation of specific olfactory pathways. The temporal relationship between primary olfactory nerve ingrowth and mitral cell and secondary olfactory pathway 9-OE expression will be determined in normal tadpoles and tadpoles in which the olfactory placodes have been removed. This experiment will test whether 9-OE expression is independently regulated in the bulb and epithelium or whether expression is each of these tissues is regulated through interaction with the other tissue. The specificity of 9-OE for VNO neurons in other mammalian species will be determine and the developmental appearance of 9- OE expression in the rate will be analyzed. The functional role of the 9- OE carbohydrate group and also other carbohydrate groups unique to olfactory system adhesion molecules will be tested first by assaying the effects of antibodies to these groups on olfactory axon outgrowth and fasiculation using in vitro assays. Then their position of attachment to the polypeptide backbone will be mapped to determine if its is similar to the position of other carbohydrate groups known to influence adhesive function. As three of the previously developed reagents which identify olfactory neuron subsets also react with carbohydrate groups on adhesion molecules, we will deliberately isolate olfactory adhesion molecules using methods which isolate the entire population and produce new monoclonal antibodies to them in order to determine if additional olfactory neuron subsets can be identified by diversity in their adhesion molecule composition.
The final aim of the proposal is to analyze the developmental relationships between the olfactory placode/epithelium and the olfactory bulb/forebrain. Using two new models of olfactory development, the small eye and legless mouse lines, the development of the olfactory bulb in the presence of abnormal epithelial development will be examined.
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