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Key factor in brain development revealed, offers insight into disorder
Date:3/26/2008

In the earliest days of brain development, the brains first cells neuroepithelial stem cells -- divide continuously, producing a population of cells that eventually evolves into the various cells of the fully formed brain. Now, scientists have identified a gene that, in mice, is critical for these stem cells to divide correctly. Without it, they fail to divide, and die.

The finding offers insight into the first steps of brain development, and may shed light, the scientists say, on a rare pediatric disorder known as lissencephaly, or smooth brain disease.

The senior author of the study was Anthony Wynshaw-Boris, MD, PhD, the recently recruited chief of the Division of Genetics in the Department of Pediatrics, and the Institute for Human Genetics at the University of California, San Francisco. He carried out the research while a professor at the University of California, San Diego. Several co-authors of the study moved with Wynshaw-Boris to the UCSF lab.

Scientists have known that loss of one of the two copies of the human form of the gene, known as LIS1, prevents immature nerve cells from migrating from deep in the brain up to the surface of the emerging cerebral cortex. These immature cells, produced from so-called radial glial progenitor cells which in turn evolve from neuroepithelial stem cells stall at mid point in their migration, creating a thick layer of tissue.

As a result, the cerebral cortex, lacking an influx of properly connected nerve cells, develops a smooth surface, devoid of convoluted nerve tissue. The resulting disease, lissencephaly, varies in severity, but often leads to retardation, seizures and early childhood death.

Scientists have had evidence that, in addition to their role in migration in immature nerve cells, the human and mouse forms of the gene may play a role in cell division and proliferation processes in radial glial progenitor cells. However, scientists have not known what th
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Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
Source:Eurekalert  

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