Scientists Identify Critical Gene for Brain Development, Mental Retardation

by Rajashri on  September 7, 2009 at 8:16 PM Genetics & Stem Cells News   - G J E 4
 Scientists Identify Critical Gene for Brain Development, Mental Retardation
A brain protein, called srGAP2, plays a vital role in brain development and could even lead to mental retardation, according to researchers at the University of North Carolina at Chapel Hill School of Medicine.

Any flaw while establishing the neural circuitry of the developing brain could result in neurodevelopmental disorders such as mental retardation, dyslexia or autism.

Researchers have now discovered that establishing the neural wiring necessary to function normally depends on the ability of neurons to make finger-like projections of their membrane called filopodia.

And the finding indicates that the current notion regarding how cells change shape, migrate or differentiate needs to be revisited.

Senior study investigator Dr. Franck Polleux said that scientists have thought that the only way for a cell to morph and move is through the action of the cytoskeleton or the scaffold inside the cell, pushing membrane forward or sucking it in.

But his study has shown that the brain protein srGAP2 can also impose cell shape by directly bending membranes, forming filopodia as a mean to control the migration and branching of neurons during brain development.

Interestingly, srGAP2 is one of a family of proteins that have been implicated in a severe mental retardation syndrome called the 3p- syndrome.

Therefore this research could also yield important insights into the underlying causes of this and other forms of mental retardation.

Polleux and his colleagues began looking at srGAP2 because the gene was almost exclusively "turned on" or expressed during brain development.

The researchers focussed on the F-BAR domain, one of the handful of similarly termed "BAR domains" in the brain protein.

These unique domains are small functional chunks of protein sequence that may be common to other proteins as well.

The researchers were among the first to master a laboratory technique that enabled them to manipulate which genes are turned on or off in neurons, a notoriously difficult cell type.

Working with slices of mouse brain, they used electrical current to introduce pieces of genetic material that would either ramp up or, conversely, knock down the action of the protein's F-BAR domain.

They then cultured brain slices in petri dishes allowing researchers to watch how the neurons behaved 'in the wild' in their native environment.

After ramping up the activity of the domain, they saw that the neurons formed the finger-like filopodia which blocked migration by inducing too many branches.

"The textbook notion is that F-BAR proteins fold inward, but here we show it can do the opposite. This is a completely novel mechanism for producing filopodia," said Polleux.

The researchers then found that when they reduced the expression of this protein, the neurons migrated at a faster rate and branched less.

The study has been published in a recent issue of the journal Cell.

Source: ANI

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