PT  - JOURNAL ARTICLE
AU  - Makoto Ohmoto
AU  - Masafumi Jyotaki
AU  - J. Kevin Foskett
AU  - Ichiro Matsumoto
TI  - Sodium taste cells require <em>Skn-1a</em> for generation and share molecular features with sweet, umami, and bitter taste cells
AID  - 10.1523/ENEURO.0385-20.2020
DP  - 2020 Nov 18
TA  - eneuro
PG  - ENEURO.0385-20.2020
4099  - http://www.eneuro.org/content/early/2020/11/17/ENEURO.0385-20.2020.short
4100  - http://www.eneuro.org/content/early/2020/11/17/ENEURO.0385-20.2020.full
AB  - 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–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–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–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.