Downregulation of L1 perturbs neuronal migration and alters the expression of transcription factors in murine neocortex.
Downregulation of L1 perturbs neuronal migration and alters the expression of transcription factors in murine neocortex.
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DOI：
10.1002/jnr.23141
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发表时间：
2013-01
影响因子：
4.2
通讯作者：
Fushiki, Shinji
中科院分区：
文献类型：
--
作者：
Kishimoto, Tomokazu;Itoh, Kyoko;Umekage, Masafumi;Tonosaki, Madoka;Yaoi, Takeshi;Fukui, Kenji;Lemmon, Vance P.;Fushiki, Shinji
L1是一种与人类神经系统疾病相关的细胞粘附分子，最著名的是X连锁脑积水。L1基因敲除（L1-KO）小鼠已经揭示了L1在不同脑区的脑发育中的各种功能。然而，在皮质组织发生过程中，L1在神经元迁移中的功能仍有待澄清。因此，我们研究了小鼠胚胎的皮质发生，其中L1分子在选定的神经元中被敲低，通过采用子宫内电穿孔与靶向L1的shRNA（L1 shRNA）。虽然在胚胎第13天（E13），超过50%的细胞转染无小发夹RNA（shRNA;怪物绿色荧光蛋白：MGFP仅）载体到达皮质板在E16，显着较少（27%）的细胞转染L1 shRNA迁移到相同的程度。在E17时，在中间区发现22%的仅用MGFP载体转染的细胞，并且显著更多（34%）的用L1 shRNA转染的细胞保持在同一区。此外，L1 shRNA转染的神经元的主导过程的方向变得更加分散，与只携带MGFP的细胞相比。此外，在神经元中表达的两种转录因子Satb 2和Tbr 1在转染L1 shRNA的神经元中显示出减少或异常表达。这些观察结果表明，L1在调节迁移神经元的运动和方向以及新皮层发育过程中转录因子的表达方面起着重要作用，这可能是L1-KO小鼠中出现的异常道形成的部分原因。© 2012 Wiley Periodicals，Inc.
L1 is a cell adhesion molecule associated with a spectrum of human neurological diseases, the most well-known being X-linked hydrocephalus. L1 knockout (L1-KO) mice have revealed a variety of functions of L1 that were crucial in brain development in different brain regions. However; the function of L1 in neuronal migration during cortical histogenesis remains to be clarified. We therefore investigated the corticogenesis of mouse embryos in which L1 molecules were knocked down in selected neurons, by employing in utero electroporation with shRNAs targeting L1 (L1 shRNA). Although more than 50% of the cells transfected with no small hairpin RNA (shRNA; monster green fluorescent protein: MGFP only) vector at embryonic day 13 (E13) reached the cortical plate at E16, significantly fewer (27%) cells transfected with L1 shRNA migrated to the same extent. At E17, 22% of cells transfected with the MGFP-only vector were found in the intermediate zone, and significantly more (34%) cells transfected with L1 shRNA remained in the same zone. Furthermore, the directions of the leading process of neurons transfected with L1 shRNA became more dispersed compared with cells with the MGFP-only vector. In addition, two transcription factors expressed in the neurons, Satb2 and Tbr1, were shown to be reduced or aberrantly expressed in neurons transfected with L1 shRNA. 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 that might partially be responsible for the abnormal tract formation seen in L1-KO mice. © 2012 Wiley Periodicals, Inc.
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影响因子：
1.2
作者：
Leid, M;Ishmael, JE;Dollé, P
通讯作者：
Dollé, P
DOI：
10.1073/pnas.1002285107
发表时间：
2010-07-20
影响因子：
11.1
作者：
Bedogni, Francesco;Hodge, Rebecca D.;Hevner, Robert F.
通讯作者：
Hevner, Robert F.
影响因子：
3.4
作者：
Britanova, O;Akopov, S;Tarabykin, V
通讯作者：
Tarabykin, V
影响因子：
11.4
作者：
Castellani, V;De Angelis, E;Rougon, G
通讯作者：
Rougon, G
影响因子：
16.2
作者：
Castellani, V;Chédotal, A;Rougon, G
通讯作者：
Rougon, G