Symmetry is an inherent part of development. As an embryo, an organism's brain and spinal cord, like the rest of its body, organize themselves into left and right halves as they grow. But a certain set of nerve cells do something unusual: they cross from one side to the other. New research in mice delves into the details of the molecular interactions that help guide these neurons toward this anatomical boundary.
In an embryo, a neuron's branches, or axons, have special structures on their tips that sense chemical cues telling them where to grow. The new findings, by researchers at Memorial Sloan Kettering Cancer Center and The Rockefeller University, reveal the structural details of how one such cue, Netrin-1, interacts with two sensing molecules on the axons, DCC and a previously less well characterized player known as neogenin, as a part of this process.
"Our work provides the first high-resolution view of the molecular complexes that form on the surface of a developing axon and tell it to move in one direction or another," says Dimitar Nikolov, a structural biologist at Memorial Sloan Kettering. "This detailed understanding of these assemblies helps us better understand neural wiring, and may one day be useful in the development of drugs to treat spinal cord or brain injuries."
In a developing nervous system, the signaling molecule, Netrin-1, identified by Rockefeller University Professor Marc Tessier-Lavigne and colleagues, can guide neurons by attracting or repulsing them. In the case of axons that cross from one side to the other, extended by so-called commissural neurons, Netrin-1 attracts them toward the middle.
With a technique that uses X-rays to visualize the structure of crystalized proteins, research scientist Kai Xu and colleagues in Nikolov's laboratory revealed that Netrin-1 has two separate binding sites on opposite ends, enabling it to simultaneously bind to different receptors. This may explain how Ne
|Contact: Zach Veilleux|