BOSTON, July 18 (UPI) -- By mutating a single gene, researchers have created mouse embryos with abnormally enlarged brains, each with the ridges and grooves normally found only in human's wrinkly "gray matter" and other advanced brains.
Although the team from two Boston hospitals has not yet grown these embryos into supergenius rodents, the researchers said their work could shed light on everything from brain tumors and mental retardation to the evolution of intelligence.
"This give us an idea on how nature might put together a large brain," co-researcher Anjen Chenn, a pathologist at Brigham and Women's Hospital, told United Press International. "This could provide clues if you want to repair or replace brain cells that have been damaged."
The largest piece of the human brain is the cerebral cortex, where the intellect is headquartered. It is a sheet of neurons or nerve cells only slightly thicker than an orange peel. Yet it accounts for about two-thirds of the brain's 100 billion neurons. It is the source of the greatly increased neural activity that distinguishes humans from mice and other, simpler mammalian brethren.
"In humans, the cortex is extremely wrinkled. That's because you're fitting a much bigger sheet into a smaller area," explained co-researcher Christopher Walsh, a neurogeneticist at Beth Israel Deaconess Medical Center. "It's like taking a piece of paper and crumpling it into a ball, in terms of surface area."
Chenn and Walsh were interested in a biochemical linked to cortex growth known as beta catenin, found in virtually all mammals and many tissues in the human body, including tumors. They genetically engineered mice that possessed excessively large amounts of the protein in neural precursor cells, which in embryos divide eventually to become fully formed brain cells.
The result was mice with swelled heads and brains with about twice as much surface area as normal.
"The growth of the brain drives the growth of the skull as well," Chenn said. The mouse brains were folded in much the same way human brains are crinkled, although there were unexplained differences in surface texture. The researchers explained beta catenin does not accelerate precursor cell division or slow cell death, but rather keeps them dividing.
Because the experiment ended three to nine days before the embryos were born, Chenn said one intriguing avenue of research would be seeing if the embryos acted smarter than their normal counterparts. However, unusually large brains in humans -- a condition known as megencephaly -- are actually tied to mental retardation.
"It's probably not sufficient to make a supergenius mouse," neurobiologist Pasko Rakic at Yale University in New Haven, Conn., said of these findings, which he called "intriguing."
"The first step to more intelligence would be to make more cells, but the second step is to make sure they're in the proper order, and there are so many other steps that can go wrong," Rakic explained. "This is why it can take such a long time to evolve intelligence -- many, many mutations occur, and only very, very few of them are useful over millions of years."
Beta catenin may be one of many proteins that cause human brains to grow bigger, or it may not be involved at all, Chenn said. Future investigations could focus on the role it plays in humans, dogs and monkeys, he suggested.
Next, the researchers said they will investigate if beta catenin surplus or deficits are linked to mental retardation.
The findings are reported in the July 19 issue of the journal Science.
(Reported by Charles Choi, UPI Science News, in New York.)
