title: β-Catenin Signaling Biases Multipotent Lingual Epithelial Progenitors to Differentiate and Acquire Specific Taste Cell Fates.
abstract: Continuous taste bud cell renewal is essential to maintain taste function in adults; however, the molecular mechanisms that regulate taste cell turnover are unknown. Using inducible Cre-lox technology, we show that activation of β-catenin signaling in multipotent lingual epithelial progenitors outside of taste buds diverts daughter cells from a general epithelial to a taste bud fate. Moreover, while taste buds comprise 3 morphological types, β-catenin activation drives overproduction of primarily glial-like Type I taste cells in both anterior fungiform (FF) and posterior circumvallate (CV) taste buds, with a small increase in Type II receptor cells for sweet, bitter and umami, but does not alter Type III sour detector cells. Beta-catenin activation in post-mitotic taste bud precursors likewise regulates cell differentiation; forced activation of β-catenin in these Shh+ cells promotes Type I cell fate in both FF and CV taste buds, but likely does so non-cell autonomously. Our data are consistent with a model where β-catenin signaling levels within lingual epithelial progenitors dictate cell fate prior to or during entry of new cells into taste buds; high signaling induces Type I cells, intermediate levels drive Type II cell differentiation, while low levels may drive differentiation of Type III cells.
authors.affiliation: Department of Cell & Developmental Biology, and the Rocky Mountain Taste & Smell Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
authors.forename: Dany
authors.initials: D
authors.lastname: Gaillard
authors.affiliation: Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America; Department of Cell & Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Mingang
authors.initials: M
authors.lastname: Xu
authors.affiliation: Institute for Regenerative Medicine at Scott & White Hospital, Texas A&M University System Health Science Center, Temple, Texas, United States of America.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Millar
authors.affiliation: Department of Cell & Developmental Biology, and the Rocky Mountain Taste & Smell Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Barlow
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction; D013649:Taste / Q000235:genetics*; D013650:Taste Buds / Q000254:growth & development* / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: D051176:beta Catenin