Genetic technologies soon gave him a way to do so. During the first decade of his studies of neuronal development, Ginty amassed a library of genes specific to different touch neuron types. Around 2007, he began genetically engineering mice in which these genes could be used to control particular populations of touch neurons. In each new mouse breed, called a line, researchers could manipulate a single type of touch neuron in all sorts of ways, such as by marking it with chemical labels to make it fluoresce, or by turning it on and off with light.
“The amount of mouse lines that were generated in David Ginty’s lab is extraordinary,” Chesler said. “He literally developed dozens of lines” and then distributed them “like Johnny Appleseed” to other researchers.
Their impact was like hearing a symphony and then suddenly being able to see and play the instruments, Chesler said. Each mouse line shone a spotlight on a different section — the strings, the winds, the brass, the percussion. “You could pick up a violin and see how it works,” he said, “or you could change the tuning or alter the instrument in some way to see how it affects the sound of the music.”
One of the first things Ginty did with his new mouse lines was explore the subterranean world of hairy skin. Non-hairy, or glabrous, skin had been relatively well studied because it houses high densities of the familiar touch players, including Merkel complexes and Meissner corpuscles. Little was known, however, about the neural structures that let you feel the bend or pluck of a hair.
Although we tend to think of skin as mostly smooth, only the palms, the soles of the feet, the lips, the nipples and portions of the genitals are truly hairless. The rest of the body is blanketed in soft, pale hairs called vellus hairs, which wick sweat to keep us cool, and thicker, more visible guard hairs, which protect the skin against damage from rubbing and scratching. As Ginty observed, each type of hair is also a touch sensor.
Using their mouse lines and other genetic tricks, his team added fluorescent tags to three populations of sensory neurons known to respond to gentle touch, but whose axon endings were still obscure. Under a microscope, the neurons lit up like neon signs, revealing their endings in the mouse’s hairy back in brilliant red and green. The researchers saw comblike projections that wrapped around hair follicles like crowns. They named the projections “lanceolate endings” after the crowns’ tapered points.
Amazingly, all three neuron populations formed lanceolate endings, but each was associated with a different type of hair. Mice have three hair types: guard hairs as well as awl and zigzag hairs, which are akin to vellus hairs in humans. Ginty’s team showed that thick, fast-conducting neurons encircle the follicles of guard and awl hairs, allowing the mice to quickly discriminate where and how they’re being touched. Meanwhile, thinner neurons that conduct signals at lower speeds target awl and zigzag hairs. Ginty later found that these neurons form one-sided crowns — more like tiaras — which convey when a hair is brushed or pulled in one direction or another. Awl and zigzag hairs are also the targets of fine, slow-conducting neurons, which were once thought to evoke tickles but have since been implicated in pleasurable touch sensations. For this reason, they are sometimes referred to as caress sensors. (These neurons also cause dogs to shake when they’re wet, Ginty’s lab recently discovered.)
Be First to Comment