Olfactory Support Cells

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Description (provided by applicant): The support cells of the olfactory epithelium have received little direct attention, yet several lines of evidence indicate that they are critical for maintaining or regulating the olfactory sensory nerve cells, the ongoing replacement of olfactory sensory nerve cells, and the local environment that allows odor detection. A detailed molecular understanding of the two major types of support cells, sustentacular cells and Bowman's gland cells, is lacking. Fortuitously, we have developed a mouse strain that will allow us to extract two dissociated cell samples: One highly enriched for sustentacular cells, the other for Bowman's gland acinar cells. Aim 1 will therefore investigate whether two support cell transcriptomes show overrepresentation of biological processes hypothesized to be active in these support cells: Clearance of foreign chemicals, cell adhesion, clearance of dying cells, secretion, and certain cell signaling pathways. The outcome of this aim will also include a database of the probability of expression in sustentacular cells and Bowman's gland acinar cells for more than 10,000 genes. Aim 2 delves more deeply into a mechanism we hypothesize controls phagocytosis by sustentacular cells, one of the few documented functions of these cells. We hypothesize that signaling through the receptor tyrosine kinase Tyro3 regulates clearance of dying nerve cells by sustentacular cells. Overall, this project is another step toward a complete understanding of gene expression patterns in the olfactory epithelium and will identify most functions present in the little-studied support cells of this tissue. In addition, these experiments are relevant to age-dependent loss of olfactory function because deficits in Tyro3 receptor family signaling in the support cells of several other tissues are known to lead to age-related disorders, such as retinal degeneration. PUBLIC HEALTH RELEVANCE: The olfactory system has evolved to detect and discriminate many thousands of distinct volatile chemicals, in part by generating a favorable microenvironment and retaining the ability to replace damaged olfactory nerve cells even as aging occurs. Investigating how the support cells of the epithelium contribute to odor detection and nerve cell replacement is bound to improve our understanding of how cellular interactions contribute to the ability of the olfactory system to function throughout an animal's life span. This project investigates the molecular capabilities of the support cells of the epithelium and a hypothesized mechanism by which support cells clear dying nerve cells to make way for new nerve cells.