Rac1 in cortical projection neurons is selectively required for midline crossing of commissural axonal formation
Rac1 in cortical projection neurons is selectively required for midline crossing of commissural axonal formation
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DOI：
10.1111/j.1460-9568.2008.06343.x
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发表时间：
2008-07-01
影响因子：
3.4
通讯作者：
Aiba, Atsu
中科院分区：
文献类型：
--
作者：
Kassai, Hidetoshi;Terashima, Toshio;Aiba, Atsu
Rac1是Rho家族GTPases的成员，通过肌动蛋白细胞骨架重组来调节多种细胞功能。在大脑皮质发生过程中，Rac 1被认为参与神经元迁移、轴突形成、极化和轴突导向。在这里，我们显示了Rac1的具体作用，调节中线交叉连合轴突在皮质发育过程中使用皮质限制Rac1基因敲除小鼠。在基因敲除小鼠中，Rac1从皮质生成的开始就被完全消除，仅在端脑背侧，皮质投射神经元的祖细胞位于端脑背侧。在基因敲除的小鼠中，皮质层只有轻微的扭曲，保留了六层神经元。然而，皮质限制性Rac1缺失表现出显着发育不全的连合轴突，包括胼胝体和前连合，而不影响其他离皮质轴突，包括皮质脊髓和皮质丘脑的预测。值得注意的是，敲除小鼠的连合轴突在延长其过程中是有效的，但未能越过中线。因此，这些研究结果表明，Rac 1专门控制中线交叉的连合纤维，但不是轴突形成皮质发育过程中的皮质脊髓或皮质丘脑纤维。
Rac1 is a member of Rho family GTPases and regulates multiple cellular functions through actin cytoskeleton reorganization. During cerebral corticogenesis, Rac1 has been assumed to be involved in neuronal migration, neurite formation, polarization and axonal guidance. Here we show the specific role of Rac1, regulating midline crossing of commissural axons during cortical development by using cortex-restricted Rac1-knockout mice. In the knockout mice, Rac1 was eliminated from the beginning of corticogenesis exclusively in the dorsal telencephalon where progenitors of cortical projection neurons are located. Cortical lamination was distorted only mildly in the knockout mice, being preserved with six layers of neurons. However, cortex-restricted Rac1 deletion exhibited striking agenesis of commissural axons including the corpus callosum and anterior commissure without affecting other corticofugal axons including corticospinal and corticothalamic projections. Of note, the commissural axons of the knockout mice were potent in extending their process, but failed to cross the midline. Therefore, these findings indicate that Rac1 specifically controls the midline crossing of the commissural fibers, but not axonal formation of corticospinal or corticothalamic fibers during cortical development.