Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons

Recently, we and others reported that the doublecortin gene is responsible for X-linked lissencephaly and subcortical laminar heterotopia. Here, we sh ow that Doublecortin is expressed in the brain throughout the period of cor ticogenesis in migrating and differentiating neurons. Immunohistochemical s tudies show its localization in the soma and leading processes of tangentia lly migrating neurons, and a strong axonal labeling is observed in differen tiating neurons. In cultured neurons, Doublecortin expression is highest in the distal parts of developing processes. We demonstrate by sedimentation and microscopy studies that Doublecortin is associated with microtubules (M Ts) and postulate that it is a novel MAP. Our data suggest that the cortica l dysgeneses associated with the loss of Doublecortin function might result from abnormal cytoskeletal dynamics in neuronal cell development.