Telling Brain Cells to Grow Up

Making a change. As they mature, neurons (stained red) switch from producing a protein called ShcA to a related protein, ShcC.

Children mature at different rates, and so do brain cells. But the proteins and signals that allow a cell to stay immature or commit to a specific fate are still unknown. Now, scientists report that a pair of proteins that helps to translate signals from the outside of the cell to the nucleus also may play a role in a cell's maturation.

A sobering fact behind all the excitement over stem cells and their possible use in new therapies is that researchers don't yet know what molecular signals control a cell's fate--information they need if they want to coax the cells to become, say, replacement neurons in Parkinson's patients. Elena Cattaneo of the University of Milan in Italy and her colleagues decided to focus on the role of a pair of proteins called ShcA and ShcC, which are part of a network of proteins that responds to external signals and helps direct the cell's reaction. The team also knew that immature, dividing cells contained ShcA, while ShcC was more prevalent in adult brain cells that can no longer divide.

Taking a closer look at the balance between the two, the researchers found a striking division: As cells in culture matured, the levels of ShcA went down and ShcC increased. In fact, ShcC was entirely absent in embryonic brain cells or in cells that were still dividing--it only appeared in mature neurons. In mature neurons in culture, extra copies of the ShcC gene increased cell survival and seemed to encourage them to grow longer neuronal extensions, the team reports in the June issue of Nature Neuroscience.

No one yet knows what controls the switch from ShcA to ShcC, but the switch might help explain why mature and immature cells respond differently to the same molecular signals, says developmental neurobiologist Mark Mehler of the Albert Einstein College of Medicine in New York City. Cattaneo says the find might someday lead to drugs that could help neurons survive in patients with neurodegenerative disorders.

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