A New Rock (as in Rho Kinase) Star

When NC State developmental biologist Nanette Nascone-Yoder says “Rockout,” she’s not asking for an air-guitar solo. Instead, she’s talking about an inhibitor of Rho Kinase (commonly known as “Rock”) that researchers use when they study particular developmental pathways.

Rho Kinase is a molecule that regulates cell shape and/or movement. It’s important to Nascone-Yoder because her research focuses on the embryonic development of the gut tube, the structure that eventually becomes our gastrointestinal tract. She uses frog embryos as a model, because the embryos are transparent and gut tube formation can be studied in real time. She is particularly interested in the ways that the gut tube lengthens, loops and coils, because when this complicated process goes awry, intestinal malformation results.

“I wanted to see the role of the Rho Kinase, or Rock, pathway in the lengthening of the gut tube, and in order to do that I needed to be able to turn that pathway off and on when and where I wanted,” Nascone-Yoder says. “While Rockout is effective in turning off Rock, we didn’t have the spatial or temporal control I needed.”

Enter chemist Alex Deiters, who is really good at photocaging molecules. When a molecule is photocaged, it is modified chemically so that it becomes photo-activatable – it turns on when it is exposed to ultraviolet (UV) light, and turns off when the light is gone. Deiters managed to photocage Rockout so that Nascone-Yoder could apply the inhibitor to the entire frog embryo, and then switch off the Rock pathway in a particular area at a particular developmental stage. She did this by focusing the UV light on areas of interest via microscope, while keeping the rest of the embryo in the dark.

“It’s similar to taking a medication that circulates throughout your body, but only activating that drug in the area that is hurting,” Nascone-Yoder says. “It’s a much better solution to the problem than trying to do genetic manipulation, and it could open up a new world of possibilities in terms of tools for studying embryonic development.”

Nascone-Yoder’s research with the photocaged Rockout appears in Development.