The sense of taste, or gustation, is mediated by taste buds, which are housed in specialized taste papillae found in a stereotyped pattern on the surface of the tongue. in embryos and discuss the cellular and molecular mechanisms governing taste cell turnover. I also spotlight how these findings aid our understanding of how and why many cancer therapies result in taste dysfunction. generation of functional taste cells from isolated lingual stem cells. For more in-depth discussions, I recommend recent reviews focused on taste bud development (Kapsimali and Barlow, 2013), taste bud innervation (Krimm et al., 2015), and the impacts of age and disease on adult taste bud homeostasis (Feng et al., 2014). An overview of the taste system Gustation is usually common to all vertebrates (Kirino et al., 2013; Northcutt, 2004). Broadly, the taste system is composed of multicellular taste buds distributed throughout the oral and pharyngeal cavities. Taste buds are innervated by sensory neurons of the VIIth, IXth and Xth cranial nerve ganglia, whose axons transmit taste information from peripheral taste buds to the hindbrain. In mammals, although some taste buds reside in the soft palate, the majority are situated around the tongue surface and are restricted to specialized taste papillae. In mammals, fungiform papillae (FFP) occupy the anterior two-thirds of the tongue and are distributed among the far more numerous non-taste filiform papillae; the latter form the tough surface of the tongue. Larger, more complex circumvallate papillae (CVP) and foliate taste papillae (FolP) are found in the posterior region of the tongue (Fig.?1). The number and pattern of taste papillae types vary in mammals (Petersen et al., 2011; Reiner et al., 2008; Witt and Miller, 1992), but rodents possess a single midline CVP, bilaterally located FolP, each containing hundreds of taste buds, and anteriorly arrayed FFP, each housing one taste bud (Fig.?1). Open in a separate windows Fig. 1. The locations of taste papillae and taste buds in the rodent tongue. Lingual taste buds are housed in distributed fungiform papillae (FFP; blue) in the anterior region of the tongue, which is otherwise covered with mechanosensory filiform papillae (flp in lower inset). Bilateral foliate papillae (FolP; blue) and a single midline circumvallate papilla (CVP; blue) are located posteriorly in the tongue. Each FFP houses one taste bud, whereas the CVP and FolP house several hundred taste buds each (depicted for the CVP only). The CVP comprises two epithelial trenches that extend ventrally from the tongue surface (asterisks in upper inset), and taste buds are aligned orthogonal to the trench axes and embedded in both medial (m) and lateral (l) trench epithelia. D, dorsal; V, ventral; A, anterior; P, posterior; R, animal’s right; L, animal’s left. In mice, taste buds comprise 60-100 elongated cells belonging to three morphological types (Types I, II and III), and at least five functional types that detect salt, sour, nice, bitter and Vatalanib free base umami (savory) (Finger and Simon, 2000; Liman et al., 2014). Type II cells detect nice, bitter or umami tastes and employ a common G protein-coupled receptor transduction cascade, which involves PLC2, IP3R3 (Itpr3) and TrpM5. However, the specific taste quality, i.e. the particular chemical signal, transduced Vatalanib free base by each Type II cell depends on the taste receptor proteins expressed. These are seven-transmembrane proteins of primarily two classes: those that detect nice, bitter or umami (T1Rs), and those that transduce bitter compounds (T2Rs). For example, sweet-sensitive Type II cells express T1R2/T1R3 heterodimers, whereas umami-sensitive Type II cells express T1R1/T1R3. Additionally, several metabotropic glutamate receptors are known to function as umami receptors (Chaudhari et al., 2000; Nakashima et al., 2012; Pal Choudhuri et al., 2015). Bitter taste is mediated by a large family of T2R proteins expressed by bitter-sensitive Type II cells (Chandrashekar et al., 2000; Liman et al., 2014). Type III cells are sour detectors and respond to acidic taste stimuli. Sour is usually thus an ionic taste and transduced via a proton current, although which transduction protein(s) are responsible remains controversial (Bushman Vatalanib free base et al., 2015; Chandrashekar et al., 2009; Huang et al., 2006). Finally, the cell type(s) mediating sodium salt taste remain ambiguous, although transduction clearly involves an epithelial sodium channel, ENaC, as well as other mechanisms (Chandrashekar et al., 2010; Oka et HNRNPA1L2 al., 2013; Roper, 2015). Type I cells are poorly comprehended, despite the fact that they make up the majority of cells within each bud (reviewed by Barlow and Klein, 2015). Morphologically, they resemble glia; they have extensive cellular processes that tightly wrap Type II and III cells (Bartel et al., 2006; Miura et al., 2014; Pumplin et al., 1997). Type I cells express membrane-localized NTPDase2 (Entpd2), an ectoATPase that converts ATP to ADP. Type II cells use ATP as a neurotransmitter to signal to sensory nerves (Finger et al., 2005; Vatalanib free base Vandenbeuch et al., 2015), yet Type II cells lack presynaptic specializations;.