Scientists have succeeded in making brainier mice. Whether the animals were actually smarter remains unknown, but their cerebral cortex surface area was significantly larger than that of normal mice. The findings, published today in the journal Science, may help explain how human brains came to be disproportionately large compared to those of other species.

As the largest structure in the brain, the cerebral cortex harbors two-thirds of the brain's neurons in a thin layer. In humans the cortex folds in on itself in order to fit inside the skull, giving the brain a unique, wrinkled topography. To investigate what controls the surface area of the cerebral cortex, Anjen Chenn, now at Northwestern University School of Medicine, and Christopher A. Walsh of Beth Israel Deaconess Medical Center developed a line of transgenic mice. The animals carried a variant of a gene that makes a protein thought to play a role in regulating cell growth in the developing brain. "We found that in mice that overproduced the beta-catenin protein the mouse's cerebral cortex grew dramatically so that instead of a flat sheet, it folded in on itself and appeared 'wrinkled' much like it is in humans," Walsh explains. (The image to the right shows the brains of a control mouse (top) and a transgenic mouse (bottom).)

Specifically, beta-catenin was more abundant in precursor cells that become neurons. The researchers propose that the protein may act as a switch that tells the cells to keep dividing or to stop and become neurons. By causing more cell division, excess beta-catenin creates a larger cortex with a greater number of neurons. Further research is required to fully elucidate the role of beta-catenin, including studies of whether its production is aberrant in cases of mental retardation characterized by abnormally small brains.