New Class Of Molecular Cues Guides Nervous System Wiring

pitous convergence of these two lines of study, reported in the third Cell article, as opening a promising new pathway to understanding the intricacies of how the brain and nervous system wires itself.

"We know that neurons grow through a series of choice points, like driving a car to a destination," said Goodman. "You don’t just dead-reckon straight to your destination. You turn onto one road, then turn onto another, make turns at a series of intersections, and finally arrive at your destination."

Neurons, like automobile drivers, depend on road signs, adds Tessier-Lavigne, and for neurons the Slit protein is clearly an important neural road sign. "You can think of guidance molecules such the Slit protein as a sign or an arrow pointing in a particular direction," he said. "A neuron can respond to that arrow in one of three ways: be attracted into going in the direction of the arrow, be repelled into going in the other direction, or just ignore it altogether."

The growing neurons likely decide on their response to these guidance proteins through sensors or receptors on their tips, called growth cones. These receptors allow the growing neuron to "read" the sign posts in the developing brain. In the case of Slit, the researchers already have an inroad into understanding how the signal is read by the growth cone: Using Drosophila genetics, they had previously identified its repulsive receptor, Robo.

The concept of multiple responses to the same guidance molecule has already been confirmed in other axon-guiding molecules, including families known as netrins, ephrins and semaphorins, said Goodman and Tessier-Lavigne. The Slit proteins, however, constitute a new family of such proteins, offering yet another pathway for exploring the intricacies of neuronal wiring.

The HHMI scientists will devote future research efforts to exploring the control machinery of the Robo receptor and Slit, attempting to understand in detail

Contact: Jim Keeley
Howard Hughes Medical Institute

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