Tasteful development: Building taste buds 8/8/04. By Giles Newton The bitter blast of espresso coffee, the cloying sweetness of caramel, the subtle richness of sashimi, the overpowering cheesiness of gorgonzola: all are a matter of taste. While some may delight in and others avoid such flavours, it is our taste buds in the tongue that sense salt, sweet, sour, bitter and umami (glutamate), while our brains decide if we like them or not.

Despite the importance of taste to our enjoyment of food and drink, and for detecting nasty or toxic substances, relatively little is known about the genes involved in taste bud development – a situation Heiko Peters at the University of Newcastle aims to redress. "There are four sensory organs in the head – eyes, ears, nose and tongue," he says. "If you look at what research papers have been published on genes on these senses, you will find that there are lots on the eyes, fewer for the ears and nose, and very little for taste. It seems that this order reflects how most people would judge the importance of their individual senses."

A close look at the surface of the tongue (preferably with an electron microscope) shows that it is not a smooth surface, being pitted with structures of varying sizes.

The onion-shaped taste buds sit within these pits, which are termed taste papillae. At the back of the tongue, the papillae are large, deep trenches holding about 150–200 taste buds. Smaller papillae containing fewer taste buds are located on the sides of the tongue – and the tiny pits in the front third of the tongue are simple papillae that have only two taste buds each (one in the case of mice).

"Food molecules come to the papilla, and are recognised by taste receptor molecules on the surface of the taste bud cells," says Dr Peters. "We want to understand the function of genes that control the development of the papilla and the taste buds. The gene we're focusing on is the transcription factor Pax9, one of nine different Pax genes found in mammals."

The Pax gene family plays a powerful role in the development of the embryo's organs and tissues. "When I started working on Pax genes, no mutations were known in Pax9, so the obvious approach was to knock out the gene in mice." The resulting knockout mice without the gene lacked teeth, thymus, parathyroid gland, and had cleft secondary palate.

The lack of teeth in the Pax9 mutant mice stimulated human geneticists to look at people with dental abnormalities – and they quickly found that a condition called hypodontia (literally, not enough teeth) was often associated with a mutation in the human PAX9 gene.

"In many cases, when you have identified a mutation that causes a human syndrome, geneticists want to understand the function of this gene, they knock out the gene in mice to find out what it does," says Dr Peters. "Here, it was other way around."

While the lack of teeth was the most obvious feature of the Pax9 mutant mice, a closer examination showed that the taste papillae were also affected. "We've found that Pax9 is expressed in the upper layers of the tongue, the epithelium," says Dr Peters. "If Pax9 is mutated, the papillae do not form normally. But we also want to know if Pax9 also regulates the development of the taste buds themselves."

Here, the project hit a snag – the Pax9 knockout mice die before birth, probably due to cleft secondary palate. Unlike humans, mouse taste buds develop two days after birth, so Dr Peters could not tell whether the buds would have developed or not. His research team has therefore developed a new strain of mice that allows Pax9 to be inactivated in the outermost surface of the tongue only.

"The taste buds form from the tissue on the surface of the tongue – the epithelium. Signals from the layer below, called the mesenchyme, somehow instruct the epithelium to make the taste structures. We know that Pax9 expression in the mesenchyme of the secondary palate is necessary for survival. So we will leave Pax9 in the mesenchyme, and see if the taste buds start to form in the epithelium."

The genetic approach has proved successful in Dr Peters's studies of tooth development – and he has already seen a lot of similarities between teeth and taste buds. "In both situations, a molecular cross-talk between mesenchyme and epithelium regulates differentiation, induces branching events and instructs cells to proliferate or to stop growing. The principles are the same."

Eating and tasting may thus have more in common than we expected.

Dr Heiko Peters is in the Institute of Human Genetics, University of Newcastle upon Tyne.

Further reading

Dr Heiko Peters research interests