title: Induction of ectopic taste buds by SHH reveals the competency and plasticity of adult lingual epithelium.
abstract: Taste buds are assemblies of elongated epithelial cells, which are innervated by gustatory nerves that transmit taste information to the brain stem. Taste cells are continuously renewed throughout life via proliferation of epithelial progenitors, but the molecular regulation of this process remains unknown. During embryogenesis, sonic hedgehog (SHH) negatively regulates taste bud patterning, such that inhibition of SHH causes the formation of more and larger taste bud primordia, including in regions of the tongue normally devoid of taste buds. Here, using a Cre-lox system to drive constitutive expression of SHH, we identify the effects of SHH on the lingual epithelium of adult mice. We show that misexpression of SHH transforms lingual epithelial cell fate, such that daughter cells of lingual epithelial progenitors form cell type-replete, onion-shaped taste buds, rather than non-taste, pseudostratified epithelium. These SHH-induced ectopic taste buds are found in regions of the adult tongue previously thought incapable of generating taste organs. The ectopic buds are composed of all taste cell types, including support cells and detectors of sweet, bitter, umami, salt and sour, and recapitulate the molecular differentiation process of endogenous taste buds. In contrast to the well-established nerve dependence of endogenous taste buds, however, ectopic taste buds form independently of both gustatory and somatosensory innervation. As innervation is required for SHH expression by endogenous taste buds, our data suggest that SHH can replace the need for innervation to drive the entire program of taste bud differentiation.
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, CO 80045, USA Rocky Mountain Taste and Smell Center, University of Colorado School of Medicine, Aurora, CO 80045, USA Graduate Program in Cell Biology, Stem Cells and Development, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: David
authors.initials: D
authors.lastname: Castillo
authors.affiliation: Program in Craniofacial and Mesenchymal Biology and Department of Orofacial Sciences, University of California San Francisco, San Francisco, CA 94131, USA.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Seidel
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, CO 80045, USA Rocky Mountain Taste and Smell Center, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Salcedo
authors.affiliation: Department of Molecular Biology, Genentech Inc., South San Francisco, CA 94080, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Ahn
authors.affiliation: Department of Molecular Biology, Genentech Inc., South San Francisco, CA 94080, USA.
authors.forename: Frederic J
authors.initials: FJ
authors.lastname: de Sauvage
authors.affiliation: Program in Craniofacial and Mesenchymal Biology and Department of Orofacial Sciences, University of California San Francisco, San Francisco, CA 94131, USA Department of Pediatrics, University of California San Francisco, San Francisco, CA 94131, USA Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94131, USA ophir.klein@ucsf.edu linda.barlow@ucdenver.edu.
authors.forename: Ophir D
authors.initials: OD
authors.lastname: Klein
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, CO 80045, USA Rocky Mountain Taste and Smell Center, University of Colorado School of Medicine, Aurora, CO 80045, USA Graduate Program in Cell Biology, Stem Cells and Development, University of Colorado School of Medicine, Aurora, CO 80045, USA ophir.klein@ucsf.edu linda.barlow@ucdenver.edu.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Barlow
mesh_terms: D000483:Alleles; D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D003433:Crosses, Genetic; D053595:Embryonic Stem Cells; D004847:Epithelial Cells / Q000166:cytology; D004848:Epithelium / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D013629:Tamoxifen / Q000737:chemistry; D013649:Taste; D013650:Taste Buds / Q000502:physiology*; D014059:Tongue / Q000378:metabolism*
chemical_list: D053823:Hedgehog Proteins; C465570:Shh protein, mouse; D013629:Tamoxifen
keywords: Cell lineage; Mouse molecular genetics; Regeneration; Taste