Johns Hopkins scientists have discovered how two closely related proteins guide projections from nerve cells with exquisite accuracy, alternately attracting and repelling these axons as they navigate the most miniscule and frenetic niches of the nervous system to make remarkably precise connections. The discovery, reported April 28 in the journal Neuron and featured on the cover, reveals that proteins belonging to the "semaphorin" family of guidance cues are crucial for getting neuronal projections exactly where they need to be, not only across long distances, but also in the short-range wiring of tiny areas fraught with complex circuitry, such as the central nervous system of the fruit fly. Because signaling that affects the growth and steering of neuronal processes is critical for repairing and regenerating damaged or diseased nerve cells, this research suggests that a more refined understanding of how semaphorin proteins work could contribute to treatment strategies, according to Dr. Alex Kolodkin, a professor in the neuroscience department at Johns Hopkins and a Howard Hughes Medical Institute investigator. Using embryonic flies, some native (normal) and others genetically altered to lack a member of the semaphorin gene family or the receptor that binds to the semaphorin and signals within the responding neuron, the team labeled particular classes of neurons and then observed them at high resolution using various microscopy strategies to compare their axon projections. In the native developing flies, the team saw how certain related semaphorins, proteins that nerve cells secrete into the intracellular space, work through binding their plexin receptor. First, a semaphorin-plexin pair attracts a certain class of extending neurons in the embryonic fly central nervous system to assemble a specific set of target projections.
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