A matter of taste

A well-tuned sense of taste is about far more than being able to enjoy a fancy dinner—it represents a key survival mechanism, helping animals to rapidly identify potential food sources as tasty or toxic (Fig. 1).

The basic principles of how taste buds enable us to recognize the five primary flavor sensations—sweet, sour, salty, bitter and umami—are reasonably well understood. Remarkably little is known about the development and maintenance of the various sensory cell types that underlie this process, however, although evidence suggests there are many interesting discoveries waiting to be made. “Taste is an interesting system, as it is continuously renewed during the lifetime,” explains Takashi Kondo of the RIKEN Brain Science Institute in Wako. “It suggests that there is a nice underlying stem cell system.”

In a new study, Kondo and colleagues have combined computational and experimental techniques to analyze the development of type II taste cells, which detect sweetness, bitterness and umami ¹. This process is specifically mediated by numerous taste receptor calcium signaling molecules (TRCSMs), and Kondo’s team started by searching for factors that might control production of these proteins during development of taste bud bundles known as circumvallate papillae (CVP).

Starting with five different TRCSMs that are all co-expressed by the same population of type II cells, they performed a computational analysis of the DNA sequences that govern the activity for each of these genes, searching for shared binding sites used by regulatory proteins. One notable candidate was HES1, a known regulator of neural development, and multiple HES1 binding sites were observed in the mouse, rat and human versions of all five genes.

After experimentally confirming that HES1 indeed binds these regulatory sequences, the researchers demonstrated that it was expressed many cells throughout the developing CVP. However, in cells expressing TRCSMs, HES1 was localized in the cytoplasm rather than the nucleus, sequestered away from the genes that it regulates, suggesting that it acts as a repressor for genes involved in type II taste cell development. This model was further supported by the observation that CVPs in mouse embryos lacking HES1 produce much greater numbers of TRCSM-expressing cells than those in normal embryos.

The authors conclude that HES1 may be involved in maintaining stem cell identity in taste cell precursors, with export of this protein from the nucleus representing an early step in type II taste cell differentiation, and Kondo says that his team is now looking deeper into this process.