Tonosaki Madoka, Itoh Kyoko, Umekage Masafumi, Kishimoto Tomokazu, Yaoi Takeshi, Lemmon Vance P, Fushiki Shinji
Department of Pathology and Applied Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Pathology and Applied Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan ; Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
PLoS One. 2014 Jan 28;9(1):e86186. doi: 10.1371/journal.pone.0086186. eCollection 2014.
L1cam (L1) is a cell adhesion molecule associated with a spectrum of human neurological diseases, the most well-known being X-linked hydrocephalus. Although we recently demonstrated that L1 plays an important role in neuronal migration during cortical histogenesis, the mechanisms of delayed migration have still not been clarified. In this study, we found that cell locomotion in the intermediate zone and terminal translocation in the primitive cortical zone (PCZ) were affected by L1-knockdown (L1-KD). Time-lapse analyses revealed that L1-KD neurons produced by in utero electroporation of shRNA targeting L1 (L1-shRNAs) molecules showed decreased locomotion velocity in the intermediate zone, compared with control neurons. Furthermore, L1-KD neurons showed longer and more undulated leading processes during translocation through the primitive cortical zone. The curvature index, a quantitative index for curvilinearity, as well as the length of the leading process, were increased, whereas the somal movement was decreased in L1-KD neurons during terminal translocation in the PCZ. These results suggest that L1 has a role in radial migration of cortical neurons.
L1细胞粘附分子（L1）是一种与多种人类神经疾病相关的细胞粘附分子，其中最著名的是X连锁脑积水。尽管我们最近证明L1在皮质组织发生过程中的神经元迁移中起重要作用，但延迟迁移的机制仍未阐明。在本研究中，我们发现中间区的细胞运动和原始皮质区（PCZ）的终末移位受L1基因敲低（L1-KD）的影响。延时分析显示，与对照神经元相比，通过子宫内电穿孔靶向L1的短发夹RNA（L1-shRNAs）分子产生的L1-KD神经元在中间区的运动速度降低。此外，L1-KD神经元在穿过原始皮质区移位过程中显示出更长且更起伏的前端突起。在PCZ终末移位期间，L1-KD神经元的曲率指数（曲线度的定量指标）以及前端突起的长度增加，而体细胞运动减少。这些结果表明L1在皮质神经元的径向迁移中起作用。
