[Developmental disorders and their responsible genes; the genes involved in neuronal positioning]

Abstract

The mammalian neocortex is a highly ordered structure with different classes of neurons aligning in an organized radial array of six cellular layers ranging from the pial surface to the white matter. Positioning of a particular neuron at the particular cortical layer is an essential step in forming an elaborate neuronal network in the neocortex. It is important to study the molecular mechanism how neuroblasts produced reach to a particular position in the laminated structure of the brain. We took advantage of reeler mutant mouse in which the position of the neurons is abnormal. We obtained an antibody against reeler gene product which we named CR-50, by immunizing wild type embryonic brains to reeler mice. CR50 blocked neuronal positioning in the cerebellum, hippocampus and cerebral cortex. CR-50 reacted with the product of the reelin gene, which was cloned as the responsible gene for the reeler mutant. Cajal-Retzius neurons secrete CR-50 antigen/Reelin and play an important role for neuroblasts to settle to their proper position in the brain. The mutant mouse missing "disabled 1", called yotari mouse, shows similar phenotypes in both morphology and behavior to those of reeler. The information of CR-50 antigen/Reelin is considered to be transmitted inside the neuroblasts to the "disabled 1", which is an adaptor protein to Src, Fyn, Abl tyrosine kinase.