Sphingolipid signaling in olfactory mucosa

University Of Cincinnati, Cincinnati OH

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Abstract

DESCRIPTION (provided by applicant): The peripheral olfactory mucosa is a fascinating model system for several reasons. Key among these is the fact that the olfactory epithelium supports continual and regulatable neurogenesis throughout life, in contrast to the central nervous system. To understand factors that are responsible for this unique neuronal plasticity, we have used broad-based methods to detect tissue-specific and developmentally-regulated gene expression in a mouse gene expression database. We identified 105 genes that were highly expressed in the olfactory mucosa using the Incyte "competitive hybridization" microarray technology. One of these, sphingosine phosphate lyase, is involved in proliferative signal transduction pathways of yeast and mammalian cells. One of the known biological functions of the Sgpl1 protein is to cleave and degrade sphingosine 1-phosphate, which is a ceramide degradation product, as well as a potent mitogen. We have confirmed sphingosine phosphate lyase enzymatic activity in the olfactory mucosa and have localized the protein to the mature olfactory neuronal population. Therefore, we hypothesize that sphingosine-1-phosphate (S-1-P) promotes the differentiation of olfactory neuronal precursor cells into mature olfactory neurons, and degradation of S-1-P by sphingosine phosphate lyase is responsible for targeting neurons for apoptosis. We propose herein to study the function of Sgpl1 in the olfactory mucosa, using a variety of in vivo and in vitro techniques, including examination of S-1-P receptors on olfactory basal cells and mature neurons; determining the effect of exogenously-administered S-1-P on olfactory basal cell proliferation and differentiation, as well as neuronal survival; and generating a mouse in which sphingosine phosphate lyase is deleted from mature olfactory neurons.