Analyses on the pathogenesis of L1-associated hydrocephalus by knocking down L1 and TAG-1

L1是一种细胞黏附分子，与一系列人类神经系统疾病有关，但L1在皮质组织发生过程中神经元迁移中的作用尚不清楚。因此，我们利用针对L1的shRNA(L1-shRNA)在宫内电穿孔的方法，研究了L1分子在选定神经元中被击倒(L1-KD)的小鼠胚胎的皮质发生。与对照组相比，L1-KD神经元的径向迁移明显延迟，其前导突起的方向更加分散。此外，在神经元中表达的两个转录因子Satb2和Tbr1在L1-KD神经元中表达减少或异常表达。这些观察结果表明，L1在新皮质发育过程中对迁移神经元的运动和定向以及转录因子的表达起着重要的调节作用。

L1 is a cell adhesion molecule associated with a spectrum of human neurological diseases, however; the function of L1 in neuronal migration during cortical histogenesis remains to be clarified. We therefore investigated the corticogenesis of mice embryos where L1 molecules were knocked down (L1-KD) in selected neurons, employing in utero electroporation with shRNAs targeting L1 (L1-shRNA). The radial migration of L1-KD neurons was significantly delayed and the directions of the leading process of L1-KD neurons became more dispersed, compared with the control neurons. In addition, two transcription factors expressed in the neurons, Satb2 and Tbr1, were shown to be reduced or aberrantly expressed in L1-KD neurons. These observations suggest that L1 plays an important role in regulating the locomotion and orientation of migrating neurons and the expression of transcription factors during neocortical development.