Project Summary Taste buds, the primary receptor organs of the gustatory system, are the first step in relaying taste information to the brain. These sensory structures comprise a heterogeneous collection of 50-100 neuro-epithelial cells encompassing three morphological classes that together transduce taste information (i.e. sweet, bitter, sour, salt, umami) into neural code. This information directly influences dietary choice and is intimately linked to human health and disease, yet despite its importance, our understanding of how the taste system is developed and maintained remains limited. The long-term goal of this study is to uncover the molecular mechanisms that regulate taste bud development. Previously, our lab has shown that taste placode cells are exclusive taste precursor cells that differentiate in to the first taste bud cells starting around birth; however, the dynamics of this process are not entirely understood. In this study we will use well-established molecular genetic tools to elucidate the cellular and molecular mechanisms that underlie cell fate decisions within developing taste buds. Using engineered mouse lines, we will examine the lineage capacity of taste precursor cells at discrete stages of embryonic taste bud development, use an unbiased approach to identify candidate genes governing cell fate decisions in the embryonic lingual epithelium, and assess the role of the Sonic hedgehog signaling pathway in regulating the onset of taste precursor cell differentiation. Future experiments, beyond the scope of this grant, will focus on identifying the specific transcriptional regulatory mechanisms that are necessary and sufficient for taste bud differentiation under both homeostatic and regenerative conditions.