Deep thoughts. The human cerebral cortex (right) has 1000 times the surface area as that of a mouse (left).

How To Grow a Bigger Noggin

Humans can read, write, and solve problems thanks to a huge cerebral cortex. To fit this sheet of brain tissue into a reasonably sized skull, the cortex of primates is wrinkled and creased, like a carpet that's much too large for its room. No one knows what prompted the cortex's expansion during primate evolution, but experiments described in the 19 July issue of Science point to one gene that might have played a role.

Developmental neuroscientists Anjen Chenn and Christopher Walsh of Brigham and Women's Hospital and Beth Israel Deaconess Medical Center in Boston created transgenic mice that made an engineered form of ß-catenin--a ubiquitous protein that has a hand in a dizzying array of developmental processes--in developing cells of the central nervous system. Because the designer protein resisted the cellular process that normally breaks it down, it accumulated in these cells.

The resulting embryos had dramatically enlarged brains and a whopping cerebral cortex. The thickness of cortex was normal, but it had increased surface area--and folds and cavities similar to those seen in monkeys or humans. The mice died soon after birth, so the researchers do not know how the bigger brains would affect their behavior, but they suggest that increased ß-catenin expression in the brain might have been one of the evolutionary changes that led to bigger brains.

When the researchers examined the embryos more carefully, they found an abnormally large number of neural precursor cells, which give rise to several types of brain cells. The overexpressed protein apparently told cells that would normally differentiate to keep dividing. That process produces a bigger cortical “sheet,” Walsh says, “and folds seem to be a passive response to the bigger sheet.” The scientists are not sure exactly how an excess of ?-catenin spurs the neural precursor cells to proliferate.

It's possible that increased production of ß-catenin played a role in increasing brain size during evolution, says Martin Raff, a developmental biologist at University College London. But that is difficult to prove, he cautions, given the protein's complex role in so many developmental processes.

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