Researchers identify gene essential for brain development, mental retardation

In defining the neural circuits of the developing brain, billions of neurons must migrate first to correct their targets and then form complex synaptic connections with their new neighbors. If the operation fails, it can cause neurological disorders such as mental retardation, autism and dyslexia. Researchers at the University of North Carolina at Chapel Hill School of Medicine have now discovered that the creation of neural wiring is required for normal function depends on the ability of neurons called the finger like projections of their cone filopodia.

The conclusion, as the cover story of the September 4th issue of the magazine was published in the journal Cell, shows that the popular idea of how cells change shape, migrate, or differentiate must be reconsidered.

Scientists believed that the only way to transform a cell and move through the action of the cytoskeleton or scaffolding inside the cell membrane pushed forward or sucking it out, "says principal investigator of the study Franck Polleux, Ph.DD, associate professor of pharmacology at the School of Medicine at UNC.

But Polleux study shows that the brain may also be imposed srGAP2 proteins across cell membranes bend to form direct filopodia as a means of controlling migration and branching of neurons during brain development.

It is interesting to note that srGAP2 a family of proteins, with a syndrome of severe mental retardation complicated than the 3p-syndrome. Therefore, this research could also be an important light on the underlying causes of this and other forms of mental retardation.

Polleux and his colleagues began to look srGAP2 because the gene is almost exclusively "on" or rotation expressed in brain development. The protein of the brain contains a unique combination of fields - small, functional blocks of the protein sequence that may be common to other proteins as well. The star of these areas is called an F field of BAR, one of the few similar to "BAR" areas that recently a bastion of research.

The UNC researchers were among the first in a laboratory technique that allowed them to manipulate the genes that are turned on or off in neurons that control a cell type known to be difficult.

Working with slices of mouse brain, they used an electric current to pieces of genetic material, or beaten by a ramp or vice versa, you want to introduce the effect of F-BAR domain protein. Then the brain slices cultured in Petri dishes, allowing researchers to see how neurons behave "in the wild in their natural environment. Ramped When the researchers measured the activity of the area, they saw that neurons formed with a finger, such as migration inducing filopodia branches blocked too.

"The manual is an idea that F-BAR proteins once inside, but here we show that it can do the opposite," said Polleux. "This is a new process for production of filopodia .

The researchers found that reduced expression of this protein migrated neurons at a faster pace and less branched. Under the microscope, neurons move as little inchworm. Before extending the projection cell long, slender neuron, pauses, then pulls the bulging cell body behind cover again, and so on.

Polleux said the F-BAR domain srGAP2 seems to establish the amount of branching neurons undergo a review to strengthen if they want to migrate and branch if they need to establish connections with other neurons.

Since the noise in these critical connections would have a negative effect on brain development, Polleux currently working with doctors at UNC, to determine if mutations in the gene srGAP2 autism or other forms of mental retardation in addition to 3p-syndrome affected. His laboratory is also interested in determining the function of about 25 other genes, such as the F-BAR domains, many of them in the developing brain cast.