Abstract
Mouse taste receptor cells survive from 3–24 days, necessitating their regeneration throughout adulthood. In anterior tongue, sonic hedgehog (SHH), released by a subpopulation of basal taste cells, regulates transcription factors Gli2 and Gli3 in stem cells to control taste cell regeneration. Using single-cell RNA-Seq we found that Gli3 is highly expressed in Tas1r3-expressing taste receptor cells and Lgr5+ taste stem cells in posterior tongue. By PCR and immunohistochemistry we found that Gli3 was expressed in taste buds in all taste fields. Conditional knockout mice lacking Gli3 in the posterior tongue (Gli3CKO) had larger taste buds containing more taste cells than did control wild-type (Gli3WT) mice. In comparison to wild-type mice, Gli3CKO mice had more Lgr5+ and Tas1r3+ cells, but fewer type III cells. Similar changes were observed ex vivo in Gli3CKO taste organoids cultured from Lgr5+ taste stem cells. Further, the expression of several taste marker and Gli3 target genes was altered in Gli3CKO mice and/or organoids. Mirroring these changes, Gli3CKO mice had increased lick responses to sweet and umami stimuli, decreased lick responses to bitter and sour taste stimuli, and increased glossopharyngeal taste nerve responses to sweet and bitter compounds. Our results indicate that Gli3 is a suppressor of stem cell proliferation that affects the number and function of mature taste cells, especially Tas1r3+ cells, in adult posterior tongue. Our findings shed light on the role of the Shh pathway in adult taste cell regeneration and may help devise strategies for treating taste distortions from chemotherapy and aging.
Highlights
In mouse tongue taste buds are found in three types of papillae: anterior fungiform (FF), lateral foliate (FO), and posterior circumvallate (CV)
To identify Gli-family transcription factors selectively expressed in subsets of adult taste cells, we analyzed single-cell RNA-Seq data generated from Lgr5-green fluorescent protein (GFP)+ stem, Tas1r3-GFP+ type II and Gad1-GFP+ type III taste cells isolated from respective GFP-transgenic mouse strains
Using GFP+ taste cells purified by fluorescence-activated cell sorting (FACS) Gli3 was found in Lgr5-GFP+ and Tas1r3-GFP+ but not Gad1-GFP+ taste cells (Fig 1A)
Summary
In mouse tongue taste buds are found in three types of papillae: anterior fungiform (FF), lateral foliate (FO), and posterior circumvallate (CV). Each taste bud contains ~50–100 mature receptor cells classified as type I, type II, or type III cells based on morphology and markers. These cells are further classified into functional subtypes that respond to basic taste qualities of sweet, bitter, umami, sour, and salt [3,4,5]. Especially for anterior tongue, has been well-studied [6,7,8]. Canonical developmental pathways such as Wnt, sonic hedgehog (Shh), Notch, and fibroblast growth factor (Fgf) pathways drive embryonic taste papillae development [reviewed in: 2, 6, 9]. Adult taste cell regeneration is affected by aging, radiation treatment and chemotherapy, infection, and autoimmune diseases [11,12,13,14,15,16,17,18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
