Testing neurons’ crossover potential

As an embryo develops, wire-like axons sprout from cells, elongating to form networks of neurons in the brain and spinal cord. Some axons cross from one side of the body to the other, while others stay put. But how do axons know whether to cross?

Scientists have shown that axons are prompted to cross the midline by an attractant protein known as netrin-1. Now a team led by Elke Stein, Ph.D., assistant professor of molecular, cellular and developmental biology and of cell biology, has shown that DSCAM (Down syndrome cell adhesion molecule), a protein that has been linked to mental retardation, is essential for netrin-1 to exert its effects on spinal axons.

By suppressing the DSCAM gene in axons that normally cross at the midline of the mouse (see photo) and rat spinal cord during development, the Stein lab, in collaboration with Marc Tessier-Lavigne, Ph.D., of California-based Genentech, found that axons that lack DSCAM lose their “sense of direction”; they fail to grow and reach the midline. The Stein lab is now investigating whether DSCAM plays this essential role in wiring up other parts of the nervous system and the nature of its contribution to Down syndrome.