Campus & Community

Why the brains of humans are bigger

3 min read

Researchers have identified a protein that may help to explain why the brain’s cerebral cortex is disproportionately larger in humans than in other species, a finding that appears in the July 19 issue of Science and adds an important piece to the developing “blueprint” of the part of the brain responsible for the intellectual abilities that make humans unique.

The largest structure in the brain, the cerebral cortex is the headquarters of our intellect – often referred to as “gray matter.” The large surface area of the cortex houses two-thirds of the brain’s 100 billion neurons in a thin layer, only slightly thicker than the peel of an orange. In order for this expanded surface area to fit within the confines of the human skull, the cortex folds in on itself, resulting in a series of ridges and grooves that give the brain its “wrinkled” appearance. This characteristic is unique to humans.

“This study looked at how the cerebral cortex develops and the role of the beta catenin protein in cortical growth,” explains senior author Christopher A. Walsh, a neurogeneticist at Beth Israel Deaconess Medical Center who has been studying cortical development and its role in mental retardation and epilepsy for nearly 10 years.

Walsh, who is also the Bullard Professor of Neurology at the Medical School, and Anjen Chenn, a research fellow in Walsh’s laboratory and a pathologist at Brigham and Women’s Hospital, set out to investigate how and why the human cortex grows so large. Cortical development is fueled by the division of “neural precursor cells,” which are the dividing cells that eventually give rise to the brain’s neurons. Unlike cells in other tissues of the body, brain cells stop dividing and become fully formed before birth.

This study examined the role of the beta catenin protein to cortical growth. Although this protein is found in many tissues throughout the body – and is also activated in tumors – its function has not been clear. To examine whether activating beta catenin could regulate signaling in the brain’s neurons, Walsh and Chenn developed a group of transgenic mice that overexpressed beta catenin in the neural precursor cells.

“The cerebral cortex in the brain of a mouse is normally smooth and flat like a sheet,” Walsh explains, describing their findings. “We found that in the 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.”

What may be happening, says Walsh, is that in the cortex, beta catenin acts like a “switch” to tell a cell whether to keep dividing, or to stop dividing and become a neuron. Expressing more beta catenin caused more cells to continue dividing, causing the cortex to keep growing. This same mechanism, he adds, might explain why beta catenin activation is associated with tumors: Although the protein does not increase the actual speed of cell division, it prevents dividing cells from “switching off,” causing tissue to grow faster than it should.