Tracing earliest neutrons' migration.

In a vertebrate embryo, the brain develops when neurons are generated along the lining of the brain's innermost cavities, the ventricles, and migrate to the outer rim of the brain. There they settle, gradually building up the many layers of the mature brain.

Scientists know little about the earliest stages of this process. Lacking a way to identify very young neurons, researchers could not tell them from nonneuronal brain cells, known as gila.

Now, researchers at Case Western Reserve University in Cleveland have found an antibody that labels these earliest neurons in rat embryos. By attaching a fluorescent tag to the antibody, the scientists can light up immature neurons as they arise in the ventricles and move away from their birthplace.

"We think that this antibody labels an unknown and newly discovered population [of neurons] that is very widespread throughout the central nervous system," says Jerry Silver, a Case Western neuroscientist. These cells occur in the retina, the spinal cord, and the brain's cortex, Silver's team reported at the annual meeting of the Society for Neuroscience, held this week in Washington, D.C.

The immature neurons first appear around the 11th day after gestation, when the embryo is about the size of a grain of rice, explains Silver. Previously, researchers could not visualize neurons until a day later, when many were well on their way to their destinations.

Earlier studies had discovered that neurons leave the ventricles by crawling along slender cells, called radial gila, that span the brain from center to surface, like the spokes of a wheel. Other studies showed that some neurons cross the brain obliquely rather than heading straight for the outer regions.

However, Perry A. Brittis, Silver's coworker, observed that the youngest neurons do neither. Instead, each cell sends out a thin process to the brain's rim and transfers its nucleus and cellular material along that thread, much as a yo-yo moves up on its string. As the cells move, they lose these trailing processes. First described in 1970, this kind of cell migration had almost been forgotten, Silver notes.

"At that very early stage, it seems to us, this 'yo-yoing' is the easiest way for the neurons to reach the brain's surface," holds Brittis. "Days later, as the brain becomes more complex, they wander along the radial gila or in oblique directions, as was demonstrated earlier. Our antibody also captures that."

"It's a neat study," comments Dennis D. M. O'Leary, a neuroscientist at the Salk Institute for Biological Studies in La Jolla, Calif. "It shows very convincingly something that several researchers have suspected for a long time."

As cells leave the ventricles, new ones take their place, says Silver, continually replenishing the supply of immature neurons to populate the developing brain.