The long-term objective of the proposed research is to understand the molecular mechanisms underlying cell fate decisions of neurons in the olfactory epithelium. The olfactory epithelium is well-suited for these studies because it gives rise to only one kind of neuron which is functionally specified by the olfactory receptor it expresses, the specific aims are: 1) The identification of differentially expressed genes from different stages of the developing olfactory epithelium and 2) The analysis of identified candidate molecules for their potential role in olfactory neuron lineage selection and functional specification. These issues will be addressed in a vertebrate model system, the zebrafish Danio rerio. Molecules involved in neural versus non-neural cell fate decisions and in the developmental regulation of olfactory receptor expression will be identified through screening of arrayed cDNA libraries with probes derived from different developmental stages. Comparing gene expression from stages before the onset of neurogenesis with those at which neurogenesis is intense should lead to the identification of molecules involved in neural versus non-neural cell fate decisions. On the other hand, comparing cDNAs from stages at which different olfactory receptors are first expressed should allow the identification of factors involved in the developmental regulation of receptor expression and therefore the regulation of cell identity. Differentially expressed molecules will be analyzed for their potential role in cell fate decisions using a variety of methods, including in situ hybridization and transgenic zebrafish.
