Lis1 reduction causes tangential migratory errors in mouse spinal cord.
Lis1 reduction causes tangential migratory errors in mouse spinal cord.
复制标题
Lis1 减少会导致小鼠脊髓发生切向迁移错误。
DOI：
10.1002/cne.22768
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Phelps,PatriciaE
中科院分区：
文献类型：
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作者：
Moore,KatherineD;Chen,Renee;Cilluffo,Marianne;Golden,JeffreyA;Phelps,PatriciaE
人类LIS1基因突变会导致神经元异常迁移和平滑的脑表型。LIS1+/−(Pafah1b1)小鼠大脑皮层和海马结构出现分层缺陷，而纯合子突变会导致胚胎死亡。鉴于Lis1在胚胎神经元中高表达，我们假设在Lis1+/−小鼠中交感和副交感节前神经元(SPN和PPN)会出现迁移缺陷。在Lis1+/−小鼠中，与躯体运动神经元一起发生的SPN和PPN的初始径向迁移未受影响。然而，随后的背侧定向切向迁移在这些神经元的一个子集中是异常的。在所分析的所有胎龄，与Lis1+/+小鼠相比，Lis1+/−小鼠SPN和PPN的分布明显延长。异位节前神经元的单个胞体位于脊髓腹侧，其前导突沿其背侧迁移轨迹定向。在出生时，Lis1+/−SPN和PPN被分成不同的组，正确的和错误的定位在中间角。由于在P30Lis1+/−小鼠中仍然检测到错位的SPN和PPN，我们认为这些神经元过早地停止了迁移。此外，我们还发现，在Lis1+/−小鼠中，腰髓背外侧核中位于背侧的一组躯体运动神经元表现出延迟迁移。这些结果表明，许多交感和副交感神经节前神经元和部分躯体运动神经元的背侧定向切向迁移需要LIS1。J.Comp.神经。520：1198-1211,2012。©2011 Wiley期刊，Inc.
Mutations in humanLIS1cause abnormal neuronal migration and a smooth brain phenotype known as lissencephaly.Lis1+/−(Pafah1b1) mice show defective lamination in the cerebral cortex and hippocampal formation, whereas homozygous mutations result in embryonic lethality. Given that Lis1 is highly expressed in embryonic neurons, we hypothesized that sympathetic and parasympathetic preganglionic neurons (SPNs and PPNs) would exhibit migratory defects inLis1+/−mice. The initial radial migration of SPNs and PPNs that occurs together with somatic motor neurons appeared unaffected inLis1+/−mice. The subsequent dorsally directed tangential migration, however, was aberrant in a subset of these neurons. At all embryonic ages analyzed, the distribution of SPNs and PPNs inLis1+/−mice was elongated dorsoventrally compared withLis1+/+mice. Individual cell bodies of ectopic preganglionic neurons were found in the ventral spinal cord with their leading processes oriented along their dorsal migratory trajectory. By birth,Lis1+/−SPNs and PPNs were separated into distinct groups, those that were correctly, and those incorrectly positioned in the intermediate horn. As mispositioned SPNs and PPNs still were detected in P30Lis1+/−mice, we conclude that these neurons ceased migration prematurely. Additionally, we found that a dorsally located group of somatic motor neurons in the lumbar spinal cord, the retrodorsolateral nucleus, showed delayed migration inLis1+/−mice. These results suggest thatLis1is required for the dorsally directed tangential migration of many sympathetic and parasympathetic preganglionic neurons and a subset of somatic motor neurons. J. Comp. Neurol. 520:1198–1211, 2012. © 2011 Wiley Periodicals, Inc.