Figure 7. Genes related to taste system research. Source: 71. Reproduced with permission from Sci Rep. (a) The heat map of genes related to taste bud organoids development. (b) The heat map of major taste receptor genes.
4.4. Signal transduction
The development of taste is not only regulated by genes, but also by numerous signaling pathways, such as Wnt/β-catenin[113], Shh[114], Fgf[115], Notch[116], and insulin[72] (Figure 8a-b). It has been proven that the Wnt-β-catenin signaling pathway initiated the development of taste papillae[113]. Therefore, Wnt signaling plays a vital role in the development of taste buds. Shh, receptor Ptc and downstream transcriptional activator Gli1 are abundantly expressed in tongue epithelial cells on the 12th day of embryonic stage and decreased in the expression on day 18[117]. In addition, after suppressing the Shh signal, the number of tongue papillae increased, the distance between tongue papillae reduced, and normal papillary development was destroyed[118]. Moreover, the expression of Shh in fungal papillae and the formation of normal mature fungal papillae depend on signal transduction through Wnt and β-catenin. Studies have shown that the activation of Wnt/β-catenin signaling up-regulated the expression of Shh. In turn, blocking Shh signaling was accompanied by the upregulation of Wnt/β-catenin signaling[119]. It was finally confirmed that Shh is an inhibitor of the Wnt/β-catenin pathway. As early as 1999, fibroblast growth factors (FGFs) and their receptors had been detected in the developing tongue[120]. After knocking out Fgf10, the circumvallate papilla tissue of the mouse will disappear completely. But the effect on fungal papillae is reversed, that is, fungal papillae appear larger and more closely spaced. Therefore, the importance of the FGF signal transduction pathway in determining the number of CVP was determined[115]. The Notch signaling pathway has also been shown to be involved in the renewal of adult taste bud cells[121]. The authors used in situ hybridization to detect the expression of related genes in this pathway in both embryonic and adult mouse tongues. Insulin is a key molecule that regulates cell growth, energy metabolism, and synaptic plasticity. The insulin signaling pathway includes important regulatory factors such as PI3K, Akt, GSK-3ß, mTOR, MAPK, and GLUT[98]. Studies have verified that insulin plays an important role in taste cell differentiation/proliferation. There are a broad expression of IR and mTOR in mouse taste bud cells, including type I, II, III, and taste progenitor cells. Moreover, taste cell proliferation was significantly promoted after using rapamycin[72]. It is suggested that the insulin-mTOR signaling pathway may regulate the maintenance of taste bud homeostasis.
The organism is an organic whole, and any changes in molecules or substances will inevitably affect other components. Preliminary studies on these genes and pathways provide strong theoretical support for future exploration of the detailed mechanism of taste transmission, and accelerate the research of taste organoids to a certain extent.