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Detailed 3-D image catches a key regulator of neural stem cell differentiation in action

LA JOLLA, CA -- Researchers at the Salk Institute for Biological Studies in collaboration with scientists at the University of California, San Diego (UCSD) took a high resolution "action shot" of a protein switch that plays a crucial role in the development of the nervous system. Their findings, published in the Dec. 8 issue of the journal Molecular Cell, provide a template for the design of small molecule inhibitors to control that switch, a protein called Scp1, at will.

"Scp1 is an important brake that regulates the transition from neuronal precursor to mature neuron," explains senior author Joseph Noel, Ph.D, a Howard Hughes Medical Institute investigator at Salk. "Loosening the brake with an inhibitor would allow us to influence the timing of neuronal differentiation," he adds.

A finely tuned network of molecular "on" and "off" switches orchestrates the differentiation of embryonic stem cells into different tissue types. Being able to manipulate individual switches would allow scientists to nudge embryonic stem cells into becoming specific cell types, a plus for both basic research and potential therapies.

"At the moment, the differentiation of stem cells into neurons in a Petri dish is a little bit like a black box and not very efficient," explains co-author Samuel Pfaff, Ph.D., a professor in the Salk's Gene Expression Laboratory, who together with co-author Gordon Gill, Ph.D., of the Departments of Medicine and Cellular and Molecular Medicine at UCSD, found that Scp1 silences neuron-specific genes in non-neuronal cells last year. "Having a specific inhibitor would give us a lot of insight into the development of the fetal nervous system and would allow us to chemically push embryonic stem cells to acquire a neuronal fate in an informed way," adds Pfaff.

Scp1 belongs to group of proteins called small carboxyl-terminal phosphatases (SCPs) that are expressed in almost all tissues of the body. When active, Scp1 prevents
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Contact: Gina Kirchweger
Kirchweger@salk.edu
858-453-4100
Salk Institute
7-Dec-2006


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