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Changing Cortical Size and Shape
Beta-catenin may Regulate Brain Shape

Image courtesy of the Comparative Mammalian Brain Collections By Melissa Lee Phillips
Neuroscience for Kids Consultant
August 29, 2002
The cerebral cortex of the human brain is highly convoluted, meaning it has many folds and creases. These convolutions allow a large surface area of brain to fit inside our skulls. Because of this brain shape, our brains can have billions of neurons and we can still have relatively small heads! Many animals do not have brain shapes like ours. Instead, their brains are smooth, with no sulci (grooves) or gyri (the bulges seen on the outer surface). However, in a new Science paper, Anjen Chenn and Christopher A. Walsh show that the normally smooth mouse brain can become folded and convoluted, much like human brains, if the production of a certain protein is changed.

The scientists studied mice that were genetically engineered to overexpress a protein called beta-catenin. Beta-catenin was already known to be involved in mammalian brain development, and it appeared to be connected to some human cancers. Therefore, it was logical that it might be important for the regulation of cell numbers. When the researchers looked at mouse embryos that contained an excess of beta-catenin, they found that the brains were abnormally large. Additionally, the brains were now folded, and therefore had an even larger surface area. Although the surface area of these mouse brains increased, the thickness of the brain tissue remained about the same.
Chenn and Walsh were interested in why the brains were bigger. Were cells dividing more quickly? Were fewer cells dying? The answer to both of these questions was "No." During development, young cells are unspecific. In other words, they have the potential to become many different types of cells. The cells continue to divide until they "choose" to become a specific type of cell. In the engineered mice with more beta-catenin, many of the young cells chose to stay in the cell cycle and keep dividing longer than usual. Eventually, they chose to become mature neurons, but because they divided for a longer period of time, there were many more of them. This increased number of neurons resulted in a larger brain volume and in an increased surface area.

Image courtesy of Comparative Mammalian Brain Collections

Altering genes that regulate the cell cycle can increase brain volume without significant changes in brain surface area. Also, reducing the amount of cell death can increase both brain volume and surface area. However, this method also produces an increase in cortical thickness which can cause severe abnormalities in the animal. In contrast, beta-catenin appears to promote the beneficial expansion of brain surface area without the debilitating increases in brain thickness. This one protein may be very important in regulating the entire shape of the brain.

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For references and more information, see:

Chenn, A. and Walsh, C.A., "Regulation of Cerebral Cortical Size by Control of Cell Cycle Exit in Neural Precursors," Science, 297:365-369, 2002.

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