Phelps Patricia E, Rich Rachel, Dupuy-Davies Shannon, Ríos Yesenia, Wong Tina
Department of Physiological Science, UCLA, Los Angeles, California 90095-1527, USA.
Dev Biol. 2002 Apr 1;244(1):180-98. doi: 10.1006/dbio.2002.0580.
Reelin, the extracellular matrix protein missing in reeler mice, plays an important role in neuronal migration in the central nervous system. We examined the migratory pathways of phenotypically identified spinal cord neurons to determine whether their positions were altered in reeler mutants. Interneurons and projection neurons containing choline acetyltransferase and/or NADPH diaphorase were studied in E12.5-E17.5 reeler and wild-type embryos, and their final locations were assessed postnatally. While three groups of dorsal horn interneurons migrated and differentiated normally in reeler mice, the migrations of both sympathetic (SPNs) and parasympathetic preganglionic neurons (PPNs) were aberrant in the mutants. Initially reeler and wild-type SPNs were detected laterally near somatic motor neurons, but by E13.5, many reeler SPNs had mismigrated medially. Postnatally, 79% of wild-type SPNs were found laterally, whereas in reeler, 92% of these neurons were positioned medially. At E13.5, both reeler and wild-type PPNs were found laterally, but by E14.5, reeler PPNs were scattered across the intermediate spinal cord while wild-type neurons correctly maintained their lateral location. By postnatal day 16, 97% of PPNs were positioned laterally in wild-type mice; in contrast, only 62% of PPNs were found laterally in mutant mice. In E12.5-E14.5 wild-type mice, Reelin-secreting cells were localized along the dorsal and medial borders of both groups of preganglionic neurons, but did not form a solid barrier. In contrast, Dab1, the intracellular adaptor protein thought to function in Reelin signaling, was expressed in cells having positions consistent with their identification as SPNs and PPNs. In combination, these findings suggest that, in the absence of Reelin, both groups of autonomic motor neurons migrate medially past their normal locations, while somatic motor neurons and cholinergic interneurons in thoracic and sacral segments are positioned normally. These results suggest that Reelin acts in a cell-specific manner on the migration of cholinergic spinal cord neurons.
Reelin是一种细胞外基质蛋白，在reeler小鼠中缺失，它在中枢神经系统的神经元迁移中起重要作用。我们检查了表型确定的脊髓神经元的迁移途径，以确定它们在reeler突变体中的位置是否发生改变。在E12.5 - E17.5的reeler和野生型胚胎中研究了含有胆碱乙酰转移酶和/或NADPH黄递酶的中间神经元和投射神经元，并在出生后评估它们的最终位置。虽然三组背角中间神经元在reeler小鼠中正常迁移和分化，但突变体中交感神经节前神经元（SPNs）和副交感神经节前神经元（PPNs）的迁移均异常。最初，在野生型小鼠中，SPNs在躯体运动神经元附近的外侧被检测到，但到E13.5时，许多reeler小鼠的SPNs向内错误迁移。出生后，79%的野生型SPNs位于外侧，而在reeler小鼠中，92%的这些神经元位于内侧。在E13.5时，reeler和野生型PPNs均位于外侧，但到E14.5时，reeler小鼠的PPNs分散在脊髓中间，而野生型神经元正确地保持在其外侧位置。到出生后第16天，97%的PPNs位于野生型小鼠的外侧；相比之下，在突变体小鼠中，只有62%的PPNs位于外侧。在E12.5 - E14.5的野生型小鼠中，分泌Reelin的细胞位于两组节前神经元的背侧和内侧边界，但没有形成坚实的屏障。相比之下，被认为在Reelin信号传导中起作用的细胞内衔接蛋白Dab1，在与其被鉴定为SPNs和PPNs的位置一致的细胞中表达。综合这些发现表明，在没有Reelin的情况下，两组自主运动神经元都向内迁移越过其正常位置，而胸段和骶段的躯体运动神经元和胆碱能中间神经元位置正常。这些结果表明，Reelin以细胞特异性方式作用于胆碱能脊髓神经元的迁移。
