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Antioxidant controls spinal cord development
Date:9/18/2009

Researchers at the Johns Hopkins School of Medicine have discovered how one antioxidant protein controls the activity of another protein, critical for the development of spinal cord neurons. The research, publishing this week in Cell, describes a never-before known mechanism of protein control.

"This is the first time we've seen this type of chemical reaction control neuronal differentiation," says Shanthini Sockanathan, Ph.D., an associate professor at the Johns Hopkins Solomon H. Snyder Department of Neuroscience. "And it's probably not specific for motor neurons that we study, but also for development of a wide variety of neurons."

Previous research had shown that the GDE2 protein can cause immature cells in the spinal cord to differentiate into motor neurons, the nerve cells that connect to and control muscle contraction. Too little GDE2 causes motor neurons to not develop, while too much GDE2 causes them to develop too quickly, depleting progenitor pools.

"We reasoned that there must be tight control of GDE2 so we set out to look for the regulator by looking for other proteins that can bind to GDE2," says Sockanathan.

Using biochemical approaches to isolate all proteins that normally bind to GDE2 in the developing spinal cord, followed by proteomic analysis to identify all binding proteins, the research team found a few hundred proteins. One, Prdx1, had been reported by others to have tumor-suppressing abilities, which caught Sockanathan's eye for further investigation.

The team first asked if the Prdx1 protein can affect motor neuron development by removing it from developing spinal cords of chick embryos. Embryos lacking Prdx1 showed loss of motor neurons similar to that seen in embryos lacking GDE2, suggesting that indeed Prdx1 is somehow involved in motor neuron development.

To figure out how Prdx1 and GDE2 interact to cause immature cells to develop into motor neurons, the team mutated the
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Contact: Audrey Huang
audrey@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
Source:Eurekalert

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