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

David Castillo,Christina Ahn,Ophir D Klein,Kerstin Seidel,Frederic J De Sauvage,Linda A Barlow,Ernesto Salcedo

doi:10.1242/dev.107631

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.

Highlights

Taste buds are the primary receptor organs of the gustatory system
Consistent with a previous report that tamoxifen activation of K14CreER results in variably sized, mosaic patches of reporter-expressing cells in taste and nontaste lingual epithelium (Okubo et al, 2009), sonic hedgehog (SHH)-YFPcKI was detected in numerous patches throughout the non-taste lingual epithelium and in some, but not all, fungiform taste buds and papillae
Ectopic taste buds arise from K14+ progenitors and express genes required for the differentiation of endogenous taste cells Because the ectopic taste buds arise from regions of the tongue that do not generate taste buds in control mice, we investigated whether they develop via a novel process or differentiate according to the lineage progression of endogenous taste buds

Summary

Introduction

Taste buds are the primary receptor organs of the gustatory system. Each bud houses a heterogeneous collection of 60-100 taste receptor cells, which transduce five basic tastes (sweet, bitter, salt, sour and umami) into electrochemical signals that are transmitted via sensory neurons to the brain (Chaudhari and Roper, 2010). Like cells of the lingual epithelium, are continually renewed from mitotically active, cytokeratin (K) 14+ basal keratinocytes (Beidler and Smallman, 1965). This K14+ population generates postmitotic cells that enter buds and differentiate into taste receptor cells (Beidler and Smallman, 1965; Farbman, 1980; Miura and Barlow, 2010; Okubo et al, 2009; Sullivan et al, 2010). We have recently demonstrated that Shh+ basal cells are immediate precursors for all taste cell types within taste buds (Miura et al, 2014)

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