Kawano H, Ohyama K, Kawamura K, Nagatsu I
Department of Anatomy, School of Medicine, Keio University, Tokyo, Japan.
Brain Res Dev Brain Res. 1995 May 26;86(1-2):101-13. doi: 10.1016/0165-3806(95)00018-9.
Migration of dopamine (DA)-containing neurons and its guiding cues were histologically examined in the embryonic mesencephalon of normal mice. Cells immunoreactive (ir) for tyrosine hydroxylase (TH), a DA-synthesizing enzyme, were first detected on embryonic day 10 (E10) in the medio-basal part of the mesencephalon and were distributed throughout the entire length of the ventral mesencephalic wall at E12. By E14, TH-ir cells were located laterally along the ventral pial surface to form the primordia of the substantia nigra. Experiments with a single injection of bromodeoxyuridine, a thymidine analog, demonstrated that cells generated in the ventricular surface of the ventral mesencephalon at E11 migrated ventrally and then moved laterally to form the substantia nigra and the ventral tegmental area. Electron microscopic examination of the ventral mesencephalon of E12 mice disclosed that in the dorsal part ventrally migrating immature neurons made close contacts with the processes of radial glial cells. The expression of tenascin was transiently seen on radial glial processes between E10 and E13 coincident with the period of the ventral migration of mesencephalic DA neurons. By double immunostaining of E13 mesencephalon, ventrally migrating TH-ir cells were seen to be apposed to tenascin-bearing radial glial processes. On the other hand, laterally migrating neurons in the basal part of the mesencephalon were observed by electron microscopy to contact with tangentially arranged nerve fibers which were immunopositive for the 160 kDa neurofilament polypeptide at the light microscopic level from E10. Double immunostaining of E13 mesencephalon demonstrated that laterally migrating TH-ir cells were intermingled among neurofilament-ir fiber bundles. The cells of origin of the tangential nerve fibers were detected in the lateral part of the mesencephalon, when a fluorescent dye, 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI) was injected into the basal part of the mesencephalon of fixed E12 mice. The present results suggest that guiding cues of the radial migration of mesencephalic DA neurons represent processes of radial glial cells which express tenascin. On the other hand, tangentially arranged nerve fibers originating from the lateral part of the mesencephalon may provide a scaffolding along which the mesencephalic DA neurons subsequently migrate laterally to form the ventral tegmental area and the substantia nigra.
在正常小鼠胚胎中脑对含多巴胺（DA）神经元的迁移及其引导线索进行了组织学检查。在胚胎第10天（E10），首先在中脑的中基底部分检测到对酪氨酸羟化酶（TH，一种DA合成酶）免疫反应阳性（ir）的细胞，在E12时这些细胞分布于整个腹侧中脑壁。到E14时，TH免疫反应阳性细胞沿腹侧软膜表面外侧排列，形成黑质原基。用胸苷类似物溴脱氧尿苷单次注射实验表明，E11时在腹侧中脑脑室表面产生的细胞向腹侧迁移，然后向外侧移动，形成黑质和腹侧被盖区。对E12小鼠腹侧中脑的电子显微镜检查发现，在背侧，腹侧迁移的未成熟神经元与放射状胶质细胞的突起紧密接触。在E10至E13期间，在放射状胶质细胞突起上短暂观察到腱生蛋白的表达，这与中脑DA神经元腹侧迁移的时期一致。通过对E13中脑进行双重免疫染色，可见腹侧迁移的TH免疫反应阳性细胞与带有腱生蛋白的放射状胶质细胞突起相邻。另一方面，通过电子显微镜观察到，中脑基部向外侧迁移的神经元与从E10起在光镜水平对160 kDa神经丝多肽免疫阳性的切向排列的神经纤维接触。对E13中脑进行双重免疫染色显示，向外侧迁移的TH免疫反应阳性细胞混杂在神经丝免疫反应阳性的纤维束中。当将荧光染料1,1'-二辛基-3,3,3',3'-四甲基吲哚羰花青高氯酸盐（DiI）注入固定的E12小鼠中脑基部时，在中脑外侧部分检测到切向神经纤维的起源细胞。目前的结果表明，中脑DA神经元放射状迁移的引导线索是表达腱生蛋白的放射状胶质细胞的突起。另一方面，源自中脑外侧部分的切向排列的神经纤维可能提供了一个支架，中脑DA神经元随后沿着这个支架向外侧迁移，形成腹侧被盖区和黑质。
