The reelin, an extracellular glycoprotein plays important roles in neuronal migration and positioning during brain development. Reelin-deficient mice, reeler shows severe abnormalities in the lamination cerebral cortex. In addition to cerebral cortex and cerebellum, some brainstem nuclei defects have also been reported in reeler mice. Dopaminergic (DA) neurons are present in the diencephalon and in the mesencephalon that define specific subsets in terms of position and function. In the midbrain, there are three major cell groups: pars compacta of substantia nigra (SNc), the ventral tegmental area (VTA), and the retrorubral field (RRF). In reeler mice, DA neurons destined for the substantial nigra fail to migrate lateral has been documented. However, the distribution of DA cells as well as the cause of malposition in the other tyrosine hydroxylase (TH)-positive regions is not fully elucidated. Present study using TH immunohistochemistry shows that reeler mice exhibit neuronal malposition in substantia nigra par compacta (SNc, A9), ventral tegmental area (VTA, A10), and retrorubal field (RRF, A8). This abnormality was also found in Dab1-deficient, yotari mice. Brain lipid binding protein (BLBP) and RC2 labeling provide evidence that abnormal morphology of radial glial fibers is unable to guide DA neurons heading toward basal part of mesencephalon. Results from the Poly highly polysialylated neuronal cell adhesion molecule (PSA-NCAM) show that Reelin plays a role in the processes of tangential nerve fibers that guide the way to lateral part. These results suggest that reelin may function as a formation cue of processes in the radial glial and tangentially arranged fibers and the malformation affects the migration and position of mesencephalic DA neurons during development.
