Confocal laser microscopic study on the mechanism of the migration of dopamine neurons in the mouse mesencephalon.

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Dopamine neurons in the mouse embryonic mesencephalon has been shown to migrate ventrally and then laterally to form the anlage of the substantia nigra pars compacta. We have examined the migratory pattern of these neurons by using immunohistochemistry and demonstrated that the ventral migration of these neurons is guided by the radial glial fibers bearing a extracellular matrix molecule, tenascin, and lateral migration is along the nerve fibers expressing cell adhesion molecules, N-CAM-H and L1 (Kawano, Ohyama, Kawamura and Nagatsu, Dev. Brain Res. 86 : 101-103,1995) .Employing the confocal laser microscope and three dimensional computer analyzer, we have observed nerve fibers and cellular interactions between migrating dopamine neurons and guiding structure. (1) When fluorescent tracer, DiI,was injected into the ventromedial part of the paraformaldehyde-fixed E12 mesencephalon, the cells of origin of the guiding fibers were revealed tobe localized in the lateral part of the, mesencephalon (Kawano, Ohyama, Kawamura and Nagatsu, Dev. Brain Res. 86 : 101-103,1995) . (2) The sections of E12 mesencephalon were treated with double fluorescent labeling in which dopamine neurons were demonstrated with anti-tyrosine hydroxylase and guiding nerve fibers with DiI.When these preparations were observed using the confocal laser microscope, the cell bodies of immature dopaminergic neurons labeled with tyrosine hydroxylase migrated laterally in contact with DiI-labeled nerve fibers. These findings indicate that specific structures expressing specific molecules which appear in the developing brain play a key role in the neuronal migration.