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Neuronal Migration: Effects of Platelet Activating Factor on Growth Cone Collapse Investigators: During the development of the brain, neurons must move from their birthplace to their adult location. Immature neurons accomplish this task by attaching to glia and migrating over impressive distances to reach their proper destinations. Therefore key elements in this process include neuron-glia adhesive interactions and cell motility. We are interested in the process of neuronal motility, a poorly understood process that probably involves the neuronal cytoskeleton. Our approach has been to use the clues derived from the genes responsible for neuronal migration disorders and to dissect the function of these genes. For instance, the gene that is deleted in one form of lissencephaly is LIS-1. This gene encodes a subunit of a platelet-activating factor (PAF) acetylhydrolase, an enzyme that degrades PAF. Therefore one might suspect that lissencephaly results from too much PAF during the time of neuronal migration. We have found that PAF receptor activation leads to profound morphological changes in developing neuronal processes and in migrating neurons. PAF causes a neuronal growth cone collapse and a neurite withdrawal that is mediated by a change in the microtubular cytoskeleton. PAF also disturbs neuronal migration by affecting the cytoskeleton of migrating neurons in vitro, possibly suggesting a common mechanism. Therefore it is our belief that PAF is a potent modulator of the neuronal cytoskeleton and it is through this action that PAF participates in the process of neuronal migration.
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