The research team focused on a repressor protein called SMRT (silencing mediator of retinoic acid and thyroid hormone receptor), which has been shown to repress gene expression in a number of molecular pathways. By creating a strain of knock-out mice missing the SMRT gene, the team was able to pinpoint significant alterations in brain development in the absence of SMRT. These findings demonstrate the important role of this protein in preventing premature differentiation of specific brain cells from undifferentiated neural stem cells in utero.

By showing that SMRT prevents differentiation by maintaining neural stem cells in a basic stem cell state, we now have a target to study further how stem cells restrict themselves from differentiating, said first author Kristen Jepsen, Ph.D., an assistant research scientist at the UC San Diego School of Medicine.

The research team also noted that in the SMRT-deficient mice, the brain exhibited signs of excessive exposure to retinoic acid--naturally occurring vitamin A--which is a known teratogen (an agent which causes birth defects). This finding suggests that in addition to maintaining neural stem cells in a pre-differentiated state, the SMRT protein controls retinoic-acid induced differentiation and, when missing, abnormalities that mimic vitamin A exposure occur.

This finding provides scientists with one more important key to understanding how stem cells maintain their potential to grow into specific cells.

Incremental steps such as this lay the groundwork for continuing studies investigating the potential of stem cells to be used therapeutically to replace damaged or deficient cells associated with disease, said Jepsen.

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In the 1950s, Prof. Efraim Katzir of the Weizmann Institute of Science, later fourth president of the State of Israel, commenced research on the properties of proteins “ the building blocks of all biological systems. This research led to the design of simple synthetic models of proteins, called polyamino acids. His research student at the time, Prof. Michael Sela (who later became president of the Weizmann Institute and was the recipient of, among many honors, the Israel Prize), decided to test the influence of these synthetic molecules on the immune system. This research led him to the conclusion that it might be possible to use these synthetic substances to curb symptoms of MS “ an autoimmune disease in which the body's immune system attacks proteins in the fatty layer surrounding nerve fibers, preventing the conductance of electrical signals through them.

Sela, together with his student at the time, Prof. Ruth Arnon (recipient of the Israel Prize and past vice president of the Weizmann Institute and vice president of the Association of Academies of Sciences in Asia), and Dr. Dvora Teitelbaum, conducted a long series of experiments. These experiments eventually led to the development of Copaxone, and clinical trials carried out by Teva showed its efficacy in treating MS. At the end of the process, in 1996, Copaxone became the first original Israeli drug to be approved by the U.S. FDA. Today, following ten years of active sales in the U.S. and 40 countries around the world, Copaxone has made a significant contribution to the Israeli economy.

Prof. Doron Lancet's research is supported by the Nella and Leon Benoziyo Center for Neurological Diseases; the Crown Human Genome Center; and the Laub Fund for Oncogene Research. Prof. Lancet is the incumbent of the Ralph and Lois Silver Professorial Chair in Human Genomics.

The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,600 scientists, students, technicians, and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials, and developing new strategies for protecting the environment.

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