SOX2 regulation by hedgehog signaling controls adult lingual epithelium homeostasis

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


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Female
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism*
  • Male
  • Mice
  • Mice, Transgenic
  • Mouth Mucosa / cytology
  • Mouth Mucosa / metabolism*
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism*
  • Taste Buds / cytology
  • Taste Buds / metabolism*


  • Hedgehog Proteins
  • SOXB1 Transcription Factors
  • Shh protein, mouse
  • Sox2 protein, mouse