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Development. 2018 Jul 17;145(14). pii: dev164889. doi: 10.1242/dev.164889.

SOX2 regulation by hedgehog signaling controls adult lingual epithelium homeostasis.

Author information

1
Department of Cell and Developmental Biology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
2
Rocky Mountain Taste and Smell Center, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
3
Graduate Program in Cell Biology, Stem Cells and Development, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
4
Program in Craniofacial Biology and Department of Orofacial Sciences, University of California San Francisco, San Francisco, CA 94131, USA.
5
BRAIN Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
6
Department of Pediatrics, University of California San Francisco, San Francisco, CA 94131, USA.
7
Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94131, USA.
8
Department of Cell and Developmental Biology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA Linda.Barlow@ucdenver.edu.

Abstract

Adult tongue epithelium is continuously renewed from epithelial progenitor cells, a process that requires hedgehog (HH) signaling. In mice, pharmacological inhibition of the HH pathway causes taste bud loss within a few weeks. Previously, we demonstrated that sonic hedgehog (SHH) overexpression in lingual progenitors induces ectopic taste buds with locally increased SOX2 expression, suggesting that taste bud differentiation depends on SOX2 downstream of HH. To test this, we inhibited HH signaling in mice and observed a rapid decline in Sox2 and SOX2-GFP expression in taste epithelium. Upon conditional deletion of Sox2, differentiation of both taste and non-taste epithelial cells was blocked, and progenitor cell number increased. In contrast to basally restricted proliferation in controls, dividing cells were overabundant and spread to suprabasal epithelial layers in mutants. SOX2 loss in progenitors also led non-cell-autonomously to taste cell apoptosis, dramatically shortening taste cell lifespans. Finally, in tongues with conditional Sox2 deletion and SHH overexpression, ectopic and endogenous taste buds were not detectable; instead, progenitor hyperproliferation expanded throughout the lingual epithelium. In summary, we show that SOX2 functions downstream of HH signaling to regulate lingual epithelium homeostasis.

KEYWORDS:

Cell differentiation; Mouse; Progenitor proliferation; Smoothened antagonist; Taste bud

PMID:
29945863
PMCID:
PMC6078335
[Available on 2019-07-15]
DOI:
10.1242/dev.164889
[Indexed for MEDLINE]

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