Format

Send to

Choose Destination
Development. 2014 Aug;141(15):2993-3002. doi: 10.1242/dev.107631. Epub 2014 Jul 3.

Induction of ectopic taste buds by SHH reveals the competency and plasticity of adult lingual epithelium.

Author information

1
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.
2
Program in Craniofacial and Mesenchymal Biology and Department of Orofacial Sciences, University of California San Francisco, San Francisco, CA 94131, USA.
3
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.
4
Department of Molecular Biology, Genentech Inc., South San Francisco, CA 94080, USA.
5
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.
6
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.

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.

KEYWORDS:

Cell lineage; Mouse molecular genetics; Regeneration; Taste

PMID:
24993944
PMCID:
PMC4197660
DOI:
10.1242/dev.107631
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center