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Christopher A. Walsh Laboratory 

Focus - January 8th, 1999

Research Briefs: Filamin1 Gene Needed for Nerve Migration in Developing Brain

By Judy Silber PH Figure

The discovery that neurons in the cerebral cortex require filamin1--a gene known for its role in blood clotting--to migrate from their birthplace in the ventricular zone to the proper layer in the cortex, surprised researchers Jeremy Fox, graduate student at HMS; Christopher Walsh, associate professor of neurology at HMS and Beth Israel Deaconess; and their collaborators. In fact, after locating the gene's chromosomal position, the researchers ranked filamin1 last on their list of likely candidates.

In identifying filamin1's role in neuronal migration, the researchers also identified the genetic cause of a rare disease called periventricular heterotopia (PH). Magnetic resonance imaging (MRI) reveals that the brains of PH patients have structural abnormalities. Walsh says the MRIs show large neurons misplaced in the ventricular zone. Surprisingly, in spite of these obvious defects in brain formation, Walsh says, the patients have normal mental capabilities. Patients do suffer from epilepsy and, as reported in the December Neuron, the mutations in filamin1 also cause blood-related conditions, such as stroke, that were initially overlooked by the researchers.

Highly conserved among disparate organisms, filamin1 regulates the cytoskeleton, causing actin to reorganize in response to signals from the extracellular matrix. Walsh suggests that without filamin1, cells cannot change their shapes appropriately in response to the surrounding environment, causing blood clots to form in the wrong places and preventing neurons from migrating. Because the filamin1 gene is on the X chromosome, females can survive with only one good copy, while males with a mutant gene generally die before birth.


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