Sunday, April 4, 2010

Genetically Modifying Songbirds to Study Human Brain Growth


zebrafinchscan

By genetically modifying the brains of songbirds for the first time, scientists may have a devised useful new tool for studying neurological growth and healing in humans.

“Songbirds have become a classic tool for studying vocal learning and neuron replacement. This will bring those two topics into the molecular age,” said neuroscientist Fernando Nottebohm of Rockefeller University, author of a study published September 28 in the Proceedings of the National Academy of Sciences.

Nottebohm’s team successfully added fluorescent protein-producing genes to 23 zebra finches, a feat that — in the age of pet dogs clones and Alba the glow bunny — may not seem extraordinarily noteworthy at first glance. But unlike many other animals, including chickens and quail, songbirds have been remarkably hard to genetically modify. That’s frustrating to scientists, who study the birds’ ability to change their songs according to setting and experience.

That ability, known as vocal learning, is believed to rely on a version of the same neurological systems that eventually allowed a clever branch of the primate tree to acquire language and become human. It makes the birds an important model of human learning, language and neural development.

gmsongbird-nNottebohm rose to fame during the 1990s, after finding that songbirds grew new brain cells in order to learn seasonal songs. That ran contrary to the conventional neurological truth of adults having a set number of brain cells. After being dismissed as fantasy, the ability has been found throughout the animal kingdom, including in humans.

All this has made songbirds as potentially important to understanding the growth of our brains as mice are to understanding our bodies. And now, just as it’s possible to genetically modify mice, scientists might do the same in songbirds.

“When you talk about underlying mechanisms at the cellular level, you have to be able to manipulate genes. Otherwise, all your hypotheses are untestable,” said Nottebohm. “It will open the door to a whole new generation of work on vocal learning that has not been possible.”

Nottebohm’s team injected 256 zebra finch embryos with viruses that traveled into the birds’ genomes and inserted a gene that produced a fluorescent protein. When the birds hatched, cells containing the protein glowed.

The method is still in proof-of-principle stages, requiring between 10 and 20 injections per embryo. That repeated trauma could explain why just 23 of the embryos hatched, and only three passed on the genetic changes to their offspring.

“There’s got to be a better way. We’re delighted that we got it that far, but as we come to understand how this works, we would like to bring up the efficiency,” said Nottebohm.

However, the importance of the technique is not in those early numbers, but the the possibility they represent, he said.

“We can test hypotheses that might explain how and why cells in the brain are replaced,” said Nottebohm.

Images: 1. Scharff Lab 2. PNAS

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