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In case you haven't looked under the hood lately, these talents are credited to that quintessentially human section of brain, the cerebral cortex. This thin layer of neurons drapes over the top of your mental motor, and indeed there is so much of it that the cerebral cortex needs to fold into ridges and valleys.

The cortex is where you think, read and plan. Without your cortex, you would be about as smart as a brick. Well, maybe a mouse, whose cerebral cortex is so small it skips the ridges-and-valleys bit.

A section through (left) a normal embryonic mouse head and (right) a mouse making extra beta catenin protein. The cerebral cortex of the transgenic mouse has greater surface area, due to the presence of more neural precursor cells. Courtesy Anjen Chenn (see 'Regulation..." below).

Getting to the point yet?
What does this have to do with science? Simply that scientists have recently learned to enlarge the mouse cortex with genetic manipulation. It was a stunt good enough to win Anjen Chenn, associate professor of pathology at Northwestern University, the first Eppendorf and Science (magazine) prize for neurobiology.

The mice received a gene that made extra quantities of beta-catenin (a protein that helps primitive brain cells "choose" what types of cells to divide into). Since the new beta-catenin is also unusually stable, the result was a huge increase in beta-catenin levels during embryonic development.

This mattered. By the time the mice were ready to be born, their brains were two or three times normal size. And since the enlargement was primarily in the cerebral cortex, it represented a dramatic shrinking of the evolutionary -- not to mention intellectual -- gap between mice and, well, men.

The brain sells
During embryonic development, neurons in the cerebral cortex are formed by the division of neuronal precursor cells. These precursor cells resemble the even-more flexible stem cells that have become a focus of medical research in the past decade. "Stem cells are self-renewing, or can give rise to any other type of cells," says Chenn. "It remains to be seen whether neural precursor cells have the potential for making other types of cell."

How would extra beta-catenin expand the cerebral cortex? Not by increasing the rate of cell division or slowing the rate of cell death. Instead, the protein seems to change the outcome, not the rate, of cell division.

When neural precursor cells divide into similar cells, they ultimately make more brain cells.

When they divide, neural precursor cells may form identical daughter cells, or brain cells (either neurons or support cells called glia). Because precursor cells ultimately do form brain cells, you get more brain cells if the precursors initially divide into precursor cells.

A larger cortex is a sign of higher development, and indeed Chenn expects his studies to help elucidate the evolutionary development of the large-brained primates. It may also explain the development of some cancers whose cells, Chenn says, resemble neural precursors.

Rodents with real brains!
Now, we have nightmares of mega-brained mice taking over Chenn's job in the pathology department at Northwestern, or our own gigs here in the Why Files basement. But it's unclear whether the mice are unusually witty: Chenn did not test the mice for smarts -- he was more interested in brain size and development.

Still, an IQ test for the mice is in the cards, he says, if they can be born alive. "It's questionable," he warns, "because the brains are quite distorted."

And while a herd of brilliant mice applying to graduate school might be profitable to institutions of higher education, Chenn adds that "It's probably not going to be so simple, just having more brain is not a precursor to having more intellect.... It probably will depend on more than one gene, and on how the neurons connect to each other. I'd guess they will not be more intelligent."

Drat!

-- David Tenenbaum

Bibliography
Making a Bigger Brain by Regulating Cell Cycle Exit, Anjen Chenn, Science, Oct. 25, 2002.

Regulation of Cerebral Cortical Size by Control of Cell Cycle Exit in Neural Precursors, Anjen Chenn and Christopher A. Walsh Science, July 19, 2002, pp. 365-369.

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