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

小鼠胚胎中脑中的多巴胺神经元已被证明向腹侧迁移，形成黑质致密部的原基。我们用免疫组织化学方法研究了这些神经元的迁移模式，证实了这些神经元的腹侧迁移是由含有细胞外基质分子Tenascin的放射状胶质纤维引导的，而横向迁移是沿着表达细胞黏附分子N-CAM-H和L1(Kawano，Ohyama，Kawamura和Nagatsu，Dev)的神经纤维进行的。利用激光共聚焦显微镜和三维计算机分析仪，我们观察了迁移的多巴胺神经元与引导结构之间的神经纤维和细胞间的相互作用。(1)将荧光示踪剂DiI注入多聚甲醛固定的E12中脑腹内侧部，发现引导纤维的起源细胞定位于中脑外侧部(Kawano、Ohyama、Kawamura和Nagatsu，Dev)。《脑研究报告》86：101-103,1995)。(2)对E12中脑切片进行双荧光标记，其中多巴胺神经元用抗酪氨酸羟化酶标记，DII标记的神经纤维用DiI标记，激光共聚焦显微镜观察，未成熟的酪氨酸羟化酶标记的多巴胺能神经元胞体与DiI标记的神经纤维接触后，胞体横向移动。这些发现表明，在发育中的大脑中出现的表达特定分子的特定结构在神经元迁移中发挥着关键作用。

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.