Major Factor In Genetic Basis Of Brain Development Discovered

October 15, 1997

Memphis, Tenn., October 16, 1997--A landmark study published today by Nature describes for the first time a major factor in normal brain development, a unique interaction between proteins produced by two brain genes. These genes are mdab1, found in brain cells and reelin, a gene that acts as a guidepost outside brain cells. The discovery may help in the search for cancer cures and more effective treatments for brain disorders like schizophrenia, childhood epilepsy and other conditions possibly caused by mutations of these genes.

Tom Curran, Ph.D., chairman of the Department of Developmental Neurobiology at St. Jude Children's Research Hospital, led the international team that evaluated the two brain genes, mdab1 and reelin. Dr. Curran and his colleagues hypothesize that the protein products of mdab1 and reelin must interact for normal brain development to occur, based on biochemical studies of mice which have identical phenotypes and mutations in these genes.

"From our earlier discovery of the reelin gene, we suspect that it is a "guidepost" outside some brain cells. This study suggests it interacts with mdab1, possibly through one or more receptors," says Dr. Curran. "As a consequence of this interaction, a signal relay is activated inside cells as part of an intercellular communication process, so brain development proceeds as it should."

For the brain to develop normally, newly generated neurons in the cerebral cortex must migrate outward, past layers of preexisting cells. When this process is disrupted, the brain fails to become fully organized. Consequently, problems ranging from ataxia (impaired ability to coordinate movement) to severe retardation can occur. This report suggests that mutations in one or both of the mdab1 and reelin genes are at least partially responsible for the devastating effects arising from abnormal brain development.

St. Jude Children's Research Hospital, in Memphis, Tenn., was founded by the late entertainer Danny Thomas. The hospital is an internationally recognized biomedical research center dedicated to finding cures for catastrophic diseases of childhood. The hospital's work is primarily supported through funds raised by the American Lebanese Syrian Associated Charities (ALSAC). All St. Jude patients are treated regardless of their ability to pay. ALSAC covers all costs of treatment beyond those reimbursed by third party insurers, and total costs for families who have no insurance.

St. Jude Children's Research Hospital

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