@article {OhmotoENEURO.0385-20.2020, author = {Makoto Ohmoto and Masafumi Jyotaki and J. Kevin Foskett and Ichiro Matsumoto}, title = {Sodium taste cells require Skn-1a for generation and share molecular features with sweet, umami, and bitter taste cells}, elocation-id = {ENEURO.0385-20.2020}, year = {2020}, doi = {10.1523/ENEURO.0385-20.2020}, publisher = {Society for Neuroscience}, abstract = {Taste buds are maintained via continuous turnover of taste bud cells derived from local epithelial stem cells. A transcription factor Skn-1a (also known as Pou2f3) is required for the generation of sweet, umami (savory), and bitter taste cells that commonly express TRPM5 and CALHM ion channels. Here we demonstrate that sodium{\textendash}taste cells distributed only in the anterior oral epithelia and involved in evoking salty taste also require Skn-1a for their generation. We discovered taste cells in fungiform papillae and soft palate that show similar but not identical molecular feature with sweet, umami, and bitter taste-mediated type II cells. This novel cell population expresses Plcb2, Itpr3, Calhm3, Skn-1a, and ENaC alpha (also known as Scnn1a) encoding the putative amiloride-sensitive salty taste receptor, but lacks Trpm5 and Gnat3. Skn-1a-deficient taste buds are predominantly composed of putative non-sensory type I cells and sour-sensing type III cells, whereas wild-type taste buds include type II (i.e., sweet, umami, and bitter taste) cells and sodium{\textendash}taste cells. Both Skn-1a and Calhm3-deficient mice have markedly decreased chorda tympani nerve responses to sodium chloride, and those decreased responses are attributed to the loss of the amiloride-sensitive salty taste response. Thus, amiloride-sensitive salty taste is mediated by Skn-1a{\textendash}dependent taste cells, whereas amiloride-insensitive salty taste is mediated largely by type III sour taste cells and partly by bitter taste cells. Our results demonstrate that Skn-1a regulates differentiation toward all types of taste cells except sour taste cells.SIGNIFICANCE STATEMENT/Author summary Salty taste plays an important role in electrolyte homeostasis in body fluids. Other basic tastes are each mediated by specialized sensory cells and elicits either preference or avoidance; in contrast, salty taste elicits both behaviors, depending on concentrations, and is mediated by multiple mechanisms and cell types that are poorly defined. We report that a subset of cells that express ENaCa exhibit a gene expression profile similar but not identical to sweet, umami, and bitter taste cells. They mediate amiloride-sensitive sodium taste and rely on Skn-1a for their generation and the CALHM ion channel for neurotransmitter release. Amiloride-insensitive salty taste is partially mediated by sour taste cells, the only taste cells present in the Skn-1a knockout mice.}, URL = {https://www.eneuro.org/content/early/2020/11/17/ENEURO.0385-20.2020}, eprint = {https://www.eneuro.org/content/early/2020/11/17/ENEURO.0385-20.2020.full.pdf}, journal = {eNeuro} }