Proteins Linked to Nerve Fiber Development

Research could lead to new treatments for brain injuries, neurodegenerative disorders.

When MIT biology ­professor Frank Gertler bred mice missing a certain set of genes, he expected their brain cells to have faulty, misrouted nerve fibers. To his surprise, he saw mutant neurons that looked like fried eggs: the somas--or cell bodies--were intact, but the branchlike dendrites and long, skinny axons were missing.

In a normal mouse embryo (top), after 16.5 days of gestation, axons are visible in red as they extend from the cortex upwards toward a part of the brain known as the internal capsule. In a mouse lacking Ena/Vasp proteins (bottom), the axons fail to grow. Credit: Adam Kwiatkowski, Doug Rubinson, Frank Gertler, Courtesy of Neuron

The typical neuron in the cerebral cortex has a single axon, which relays information to other cells, and many shorter dendrites, which receive messages from other cells. The genetically altered mice in the study produced brain cells that were unable to extend any axons or dendrites or to connect with other neurons.

The family of proteins encoded by the three genes Gertler was investigating, known as Ena/Vasp proteins, turns out to play a critical role in the development of nerve fibers. Manipulating these proteins may one day help repair spinal-­column injuries and other damage caused by faulty cell-to-cell connections. "We think that the mechanisms we have begun to unravel might open the door to potential regenerative therapies for neurodegeneration or brain injuries," Gertler says.

A cell's shape is determined by its cytoskeleton--the internal pillars and girders that push against the cell membrane. To move and change shape, a cell must remodel its cytoskeleton. "It's like the cell is reading traffic signals and trying to figure out where to go," Gertler says. Ena/Vasp proteins are the navigators for nerve outgrowths called neurites, the precursors to axons and dendrites.

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The proteins are located in the tips of a neurite's filopodia--short extensions that receive environmental signals and translate them into instructions for the cell. Those instructions tell the cell either to continue extending the filopodia, by lengthening protein filaments, or to stop growth.

"This is one of the first studies that uncover the early steps in how a differentiated neuron begins to acquire its unique morphology," Gertler says.