Reelin and Migration of Sympathetic Preganglionic Neurons

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After they finish dividing, neurons typically make long guided migrations to reach their proper loction in the brain. The reelin gene is required for normal neuronal migration on the cerebellum, and more recently it has been found to have similar effects in other brain areas such as the cerebrl cortex. However, despite the interest in this gene, it is not known whether it acts directly upon neurons or more indirectly through other intermediaries, or whether the protein product is inhibitory or stimulatory. The applicant will use a novel system to examine this problem. Preliminary data reveal that reelin regulates the migration of preganglionic sympathetic neurons and that this phenomenon can be mimicked in a simple in vitro slice system. This system will used to: 1) map the migration of pregaglionic sympathetic neurons in mice; 2) look at the spatiotemporal relationship between reelin protein and migration preganglionic neurons; and 3)use blocking antibodies and reelin producing cells to examine the biological activity of this protein. Since disorders of neural migration are common in many forms of mental retardation, this research should provide insights into the causes of these devastating disorders. Since molecules also interacts with apoE and VLDL, it could also be important in Alzheimer's disease.