Neurons let it slide

During mammalian brain development, many neurons migrate away from the site where they are born to settle in distant locations where they send out dendrites and axons to connect with other neurons. Both neuronal migration and axon/dendrite extension depend on forces generated by microtubule-based motor proteins such as cytoplasmic dynein. The effects of these forces depend, however, on the organization of the microtubule cytoskeleton. Rao et al. reveal that a small number of micro-tubules that aren't attached to the centro-some, and which can therefore undergo motor-driven sliding, help migrating neu-rons navigate toward their destination and that, when the number of these centrosome-unattached microtubules is increased, neurons come to a halt and begin extending axon-like projections (1). In migrating neurons, most, if not all, microtubules are attached to the centro-some. Many of them extend into a short leading process at the front of the cell, and, when motors pull on these micro-tubules, the centrosome is dragged forward , bringing with it the nucleus and the rest of the neuronal cell body. " The lore is that all of the functionally relevant microtubules are attached to the centrosome, " says Peter Baas, from Drexel University College of Medicine in Philadelphia, Penn-sylvania. " We decided to look, using the most rigorous techniques available, whether they are really all attached. " Baas and colleagues, led by graduate students Anand Rao and Aditi Falnikar, used electron tomography to identify micro-tubule minus ends in cerebellar granule neurons migrating in vitro and found that a small number of them weren't associated with the centrosome (1). Using EGFP-CAMSAP3, a fl uorescent marker of free microtubule minus ends, the researchers confi rmed that, indeed, a handful of unattached microtubules are present in both the leading process and cell body of migrating neurons. " Our next question was whether these unattached microtubules matter, " says Baas. " Are they functionally relevant? " Rao et al. found that motor proteins can transport, or slide, unattached micro-tubules within the leading process of migratory neurons. When the researchers added a drug to cross-link and immobilize these microtubules, the leading process grew shorter and, although the neurons still moved, they frequently changed direction instead of migrating in a simple, straight line. " So we think the sliding of this small number of centro-some-unattached micro-tubules provides maneuverability to the leading process that can correct small path-fi nding defects and keep the neuron migrating smoothly, " …