Genetic Mixer in the Developing Brain

Shuffling the deck. Random genetic changes inside some neurons (green) may ensure that every brain is unique.

Personality and talents are usually chalked up to a mysterious mix of heredity and environment. A provocative new study, however, hints at a third factor: bits of genetic material that spontaneously hop around the genome of neurons in the developing brain, altering patterns of gene expression. The scientists who discovered the phenomenon propose that it adds a random twist to neural development that ensures that no two brains--not even those of identical twins--are put together in exactly the same way.

The researchers, led by Fred Gage at the Salk Institute for Biological Sciences in La Jolla, California, were investigating how neural stem cells decide whether to turn into neurons or support cells. Searching for genes that might guide this decision, the team noticed that rat cells in the process of becoming neurons contained increased levels of RNA corresponding to so-called L1 retrotransposons, bits of DNA that can jump around in the genome, sometimes altering the activity of genes they land in.

Intrigued, the team inserted a human version of L1 into rat neural stem cells, along with a marker that would make the cells glow green whenever L1 made a jump. Many cells lit up, and when the researchers took a closer look, they found that L1 jumped into several genes typically expressed by neurons. In some cases, the jump altered gene expression in a way that influenced the stem cells' fate--making them more likely to turn into neurons, for example.

Additional experiments with transgenic mice indicated that L1 had hopscotched in a subset of brain cells, but not in the cells of most other tissues. In principle, Gage says, this process could generate distinct neural circuitry in each individual by altering the proportion of neuron types or levels of gene expression in the brain.

If L1 does prove to have an important role in brain development, that would be surprising, says Haig Kazazian, a geneticist who studies retrotransposons at the University of Pennsylvania in Philadelphia. "These are genetic parasites as far as we know, and we never thought they might have a function like this." Still, he and others say much more work will be needed to determine whether retrotransposons change the course of brain development in normal animals--let alone people. "It has the potential to open a new paradigm, but it's not there yet," Kazazian says.

Related sites
Gage's site
Kazazian's site

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