Regulation of connective tissue in the cell renewal of mature taste buds

Project Summary/Abstract Mammalian taste buds are a cluster of specialized epithelial cells residing primarily in the epithelium of the lingual taste papilla which covers a core of connective tissue. Like other epithelial cells, taste bud cells have a short lifespan and undergo continuous renewal. Therefore, the homeostasis of taste buds and taste sensation

requires constant taste bud cell differentiation from progenitors. Thorough information of the regulation in taste cell differentiation from progenitors is essential to understanding taste disorders and finding effective therapeutic treatments. Prior studies on the molecular regulation in taste cell differentiation have focused on the signals

within epithelium. Little is known regarding the roles of the underlying connective tissue. Recently, for the first time in the field, our findings demonstrated the requirement of signals from neural crest- derived tongue mesenchyme in taste papilla differentiation during embryonic development. This leads us to ask

whether the underlying connective tissue regulates the cell renewal of mature taste buds in adult animals. Our preliminary data revealed that delivery of extracted proteins from the genetically modified embryonic tongue mesenchyme into adult mouse tongue resulted in an alteration of taste buds in the injection-surrounding tongue

region. Moreover, selected signaling proteins (i.e., Noggin and Pleiotrophin) secreted by embryonic tongue mesenchyme were also detected in the neural crest-derived connective tissue cells from adult mouse tongue, suggesting a mesenchymal regulation in the homeostasis of taste buds in adult mice. We hypothesize that in adult animals the neural crest derived connective tissue cells in the core of taste

papillae send signals to the overlying epithelium and regulates cell renewal of mature taste buds. In this proposal, we will use both in vivo and ex vivo systems to examine the effects of cell products from connective tissue cells on taste cell differentiation. Neural crest-derived connective tissue cells in fungiform and circumvallate papilla

region will be sorted from adult Sox10-Cre/tdTomato (tdT) mice. The tdT+ (neural crest-derived) cells will be cultured for isolation of protein fractions (>100 kDa, 10-100 kDa,