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Taste buds, the sensory organs for taste, have been described as arising solely from the surrounding epithelium, which is in distinction from other sensory receptors that are known to originate from neural precursors, i.e., neural ectoderm that includes neural crest (NC). Our previous study suggested a potential contribution of NC derived cells to early immature fungiform taste buds in late embryonic (E18.5) and young postnatal (P1-10) mice. In the present study we demonstrated the contribution of the underlying connective tissue (CT) to  mature  taste buds in mouse tongue and soft palate. Three independent mouse models were used for fate mapping of NC and NC derived connective tissue cells: (1)  P0-Cre/R26-tdTomato (RFP)  to label NC, NC derived Schwann cells and derivatives; (2)  Dermo1-Cre/RFP  to label mesenchymal cells and derivatives; and (3)  Vimentin-CreER/mGFP  to label Vimentin-expressing CT cells and derivatives upon tamoxifen treatment. Both  P0-Cre/RFP  and  Dermo1-Cre/RFP  labeled cells were abundant in mature taste buds in lingual taste papillae and soft palate, but not in the surrounding epithelial cells. Concurrently, labeled cells were extensively distributed in the underlying CT. RFP signals were seen in the majority of taste buds and all three types (I, II, III) of differentiated taste bud cells, with the neuronal-like type III cells labeled at a greater proportion. Further,  Vimentin-CreER  labeled cells were found in the taste buds of 3-month-old mice whereas Vimentin immunoreactivity was only seen in the CT. Taken together, our data demonstrate a previously unrecognized origin of taste bud cells from the underlying CT, a conceptually new finding in our knowledge of taste bud cell derivation, i.e., from both the surrounding epithelium and the underlying CT that is primarily derived from NC.

Contribution of Underlying Connective Tissue Cells to Taste Buds in Mouse Tongue and Soft Palate