Cell-autonomous roles of ARX in cell proliferation and neuronal migration during corticogenesis
Cell-autonomous roles of ARX in cell proliferation and neuronal migration during corticogenesis
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DOI：
10.1523/jneurosci.1067-08.2008
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发表时间：
2008-05-28
影响因子：
5.3
通讯作者：
Parnavelas, John G.
中科院分区：
文献类型：
--
作者：
Friocourt, Gaeelle;Kanatani, Shigeaki;Parnavelas, John G.
马兜铃相关同源框（ARX）基因与多种疾病有关，从具有严重神经元迁移缺陷的表型，如无脑畸形，到无明显大脑异常的x连锁智力迟钝的轻度形式。为了更好地了解其在皮质发生中的作用，我们在子宫内电穿孔来敲低或过表达ARX。我们在这里表明，ARX的靶向抑制导致皮质祖细胞过早退出细胞周期，并损害它们向皮质板的迁移。相反，ARX过表达增加了细胞周期的长度。此外，我们报告了RNA干扰介导的ARX失活可阻止细胞在室下和中间区获得多极形态，导致神经元运动能力下降。相反，ARX过表达似乎促进了脑室下和中间区细胞的切向过程的发展，并影响锥体神经元的径向迁移。我们还证明，ARX的表达水平对于含有gaba的中间神经元的切向迁移很重要，因为该基因的失活和过表达都会损害它们从神经节隆起的迁移。然而，我们的数据表明，ARX并不直接参与gaba能细胞的命运规范。总的来说，这些结果确定了ARX在皮质发生中的多种不同的细胞自主作用。
The aristaless-related homeobox (ARX) gene has been implicated in a wide spectrum of disorders ranging from phenotypes with severe neuronal migration defects, such as lissencephaly, to mild forms of X-linked mental retardation without apparent brain abnormalities. To better understand its role in corticogenesis, we used in utero electroporation to knock down or overexpress ARX. We show here that targeted inhibition of ARX causes cortical progenitor cells to exit the cell cycle prematurely and impairs their migration toward the cortical plate. In contrast, ARX overexpression increases the length of the cell cycle. In addition, we report that RNA interference-mediated inactivation of ARX prevents cells from acquiring multipolar morphology in the subventricular and intermediate zones, resulting in decreased neuronal motility. In contrast, ARX overexpression appears to promote the development of tangentially oriented processes of cells in the subventricular and intermediate zones and affects radial migration of pyramidal neurons. We also demonstrate that the level of ARX expression is important for tangential migration of GABA-containing interneurons, because both inactivation and overexpression of the gene impair their migration from the ganglionic eminence. However, our data suggest that ARX is not directly involved in GABAergic cell fate specification. Overall, these results identify multiple and distinct cell-autonomous roles for ARX in corticogenesis.