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.