Abstract

The tongue epithelium is one of the most rapidly self-renewing tissues in adult mammals. Multiple stem cell populations are currently believed to exist in tongue epithelia. Keratin 14 (K14) positive cells differentiate into either lingual epithelia or lingual papillae, while ecto-nucleoside triphosphate diphosphohydrolase 2 (NTPDase2) is associated with neural stem cells and astrocyte-like cells ensheathing the migrating neuroblasts. Here, using a transgenic mouse expressing rtTA from the mouse NTPDase2 promoter, we generated an inducible model by treatment with Doxycycline. By immunohistochemical analysis and in situ hybridization, we found exclusive expression of NTPDase2 in lingual epithelia and lingual papillae. Using inducible genetic cell fate mapping, we further showed that the NTPDase2+ cells generated lingual papillae and epithelia in the adult tongue. Finally, building on our previously proposed paradigm of cell migration stream, a model is further described here for lingual epithelia cell genesis. In short, the current results not only extend our understanding of the cell migration stream in lingual epithelia and lingual papillae, but they also support the concept of multiple stem cell populations in lingual epithelia and papillae.

Highlights

  • The mouse tongue contains numerous papillae creating a specialized mucosa

  • Nongustatory oral epithelia or epidermis can be transplanted into regions innervated by taste nerve fibers, taste buds cannot be induced in these epithelia even in the presence of nerves that have the capacity to induce them in appropriate epithelia (Zalewski, 1972)

  • These observations collectively indicate that certain factors may be pre-stored in lingual epithelia and lingual papillae to facilitate this regeneration, as suggested that placodes go through morphogenesis to form the taste papillae with interaction to a mesenchymal core from embryonic day 12 to post natal day 4 in mice (Thirumangalathu and Barlow, 2009; Thirumangalathu et al, 2009), and since a population of taste bud stem cells is established within the local epithelium via local cell–cell interactions (Barlow et al, 1996; Barlow and Northcutt, 1997)

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Summary

Introduction

The mouse tongue contains numerous papillae creating a specialized mucosa. The three main types are circumvallate (CV; Figure 1A), fungiform (Figure 1B), and filiform papillae (Figures 1B,C). Taste buds are present on fungiform (Figure 1B), CV (Figure 1A), and foliate papillae (Figure 1D; Ross and Pawlina, 2006). In all cases, they arise during development from the local surface epithelium rather than from neuronal or neural crest cells (Stone et al, 1995, 2002). Studies have shown that both the receptor cells of the taste buds and the stratified keratinized epithelium of the fungiform papillae in which they reside, as well as the numerous filiform papillae of the tongue, are all derived from the same simple epithelium present in the embryo (Farbman, 1965a; Baratz and Farbman, 1975). The terminally differentiated cells of the epidermis cannot divide, and their replacement depends on less highly differentiated cells, i.e., stem cells

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