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Xinzhong Dong of Neuroscience
on the molecules behind the itch:
Can you describe the types of genes that your lab studies and how you became interested in them?
DONG: The genes we study are expressed with high specificity in dorsal root ganglia (DRG) neurons. We think that these genes are interesting because if a gene is expressed specifically in a certain tissue, it must have some specific function there, or it would have been lost during evolution. This specificity also allows us to really narrow down our problem, because the cell type is very important for the behavioral phenotype. If you see a behavioral effect, but the genes you are studying are expressed in many places in the body, you don’t know where to look for the gene to determine the function.
What are some of the advantages of studying neurons in the dorsal root ganglia (DRG) in particular?
DONG: One advantage is that knockout genes expressed in DRG neurons are not lethal. Even if you delete the entire DRG, it’s not that critical. Animals don’t seem to need pain-sensing neurons, so you can always get animals to survive into adulthood, you can do straight knockouts, and you can study behavior in those animals. In contrast, if you want to knock out genes in the central nervous system, you have to do conditional knockouts, and the promoters to drive those conditional knockouts may not be specific. The behavior for studying processes mediated by the central nervous system, like learning and memory, is also very complicated. Pain and itching behavior is relatively easy to study, and it’s already complicated.
Can you describe your recent work into the perception of gentle touch?
DONG: We published a paper studying the projection pattern of one of the genes we identified that is highly specific and expressed in DRG neurons. We don’t have functional data yet, but based on previous studies, we think that neurons expressing this gene might mediate gentle touch. This gene, MrgB4, is expressed in only about 1 to 2 percent of DRG neurons. When we traced MrgB4-expressing neurons to see where they project, we found that they project only to the hairy skin, as opposed to the hairless skin found on the palms of your hands. The innervation pattern is quite random and patchy, with a big receptor field. It’s really quite striking—the whole animal looks just like a cow. Previous studies in humans, cats, and other mammals have suggested that tactile sensation is mediated by unmyelinated C-fibers, and these fibers show similar characteristics to the MrgB4-expressing neurons we described. They only innervate the hairy skin, and their receptor field is very big, just like we found. In the paper we proposed that we had identified a subset of DRG neurons that mediate tactile sensation, but if we want to prove it, we have to get rid of those neurons and look at the effects.
What are your long-term research goals?
DONG: Of course, in the long term we want to move this to a higher order in the brain and see where these different types of sensation are really generated. Are itching and pain generated in the same cortical regions in the brain or in different regions? My bet is different regions, because the behavioral response is very different. With itching you scratch and with pain you withdraw. But we want to go from the simplest system first—the DRG is relatively simple. We want to find molecular markers and specifically label these neurons so we can manipulate them molecularly or genetically and answer some key questions. I think it’s a good field to work on because you are involved in every discipline in neuroscience. You can work from dissociated neurons to animals, you can do knockouts, imaging, recording, behavior. There are not many labs that can apply all of those disciplines into one problem.