Extension of long leading processes and neuronal migration in the mammalian brain directed by the chemoattractant netrin-1

Long distance cell migration occurs throughout the developing CNS, but the underlying cellular and molecular mechanisms are poorly understood. We show that the directed circumferential migration of basilar pontine neurons fro m their origin in the neuroepithelium of the dorsal hindbrain to the ventra l midline involves the extension of long (>1 mm) leading processes, which m arker analyses suggest are molecularly distinct from axons. In vivo analysi s of knockout mice implicates the axonal chemoattractant netrin-1, function ing via its receptor Deleted in Colorectal Cancer (DCC), in attracting the leading process to the ventral midline. Direct evidence for this chemoattra ctant mechanism is provided, using explant cultures and time-lapse analysis in vitro. Our results demonstrate the attraction of migrating neurons in t he mammalian brain by an axon guidance molecule and the chemotactic respons iveness of their leading processes.