Essential role of Rac1 and Rac3 GTPases in neuronal development
Essential role of Rac1 and Rac3 GTPases in neuronal development
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DOI：
10.1096/fj.08-121574
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发表时间：
2009-05-01
期刊：
影响因子：
4.8
通讯作者：
de Curtis, Ivan
中科院分区：
文献类型：
--
作者：
Corbetta, Sara;Gualdoni, Sara;de Curtis, Ivan
Rac GTP酶是Rho家族的成员，调节肌动蛋白细胞骨架并参与神经元发育。普遍存在的Rac1和神经元特异性Rac3 GTP酶在发育中的哺乳动物大脑中共表达。我们使用Cre介导的Rac 1在神经元中的条件性缺失结合敲除神经元特异性Rac 3来研究这些GTP酶在神经发育中的作用。我们发现，这两种基因的缺乏会导致运动行为缺陷、癫痫和小鼠过早死亡。任何一个GTdR的缺失都不会产生明显的表型。双基因敲除小鼠在海马体发育中表现出特定的缺陷。双基因敲除动物背门的选择性损伤与海马回路形成的改变有关。由于门苔藓细胞的缺陷，来自背门的轴突通路受到影响。此外，在海马培养的Rac功能的分析表明，脊柱的形成强烈阻碍只有在神经元缺乏Rac蛋白。这些发现首次表明Rac 1和Rac 3对神经系统的发育都很重要，它们在神经元和大脑发育的后期发挥互补作用。科尔贝塔，S.，Gualdoni，S.，Ciceri，G.，Monari，M.，Zuccaro，E.，蒂布勒维奇J.，德柯蒂斯岛Rac 1和Rac 3 GTP酶在神经元发育中的重要作用FASEB J. 23，1347 - 1357（2009）
Rac GTPases are members of the Rho family regulating the actin cytoskeleton and implicated in neuronal development. Ubiquitous Rac1 and neuron-specific Rac3 GTPases are coexpressed in the developing mammalian brain. We used Cre-mediated conditional deletion of Rac1 in neurons combined with knockout of neuron-specific Rac3 to study the role of these GTPases in neural development. We found that lack of both genes causes motor behavioral defects, epilepsy, and premature death of mice. Deletion of either GTPase does not produce evident phenotypes. Double-knockout mice show specific defects in the development of the hippocampus. Selective impairment of the dorsal hilus of double-knockout animals is associated with alteration in the formation of the hippocampal circuitry. Axonal pathways to and from the dorsal hilus are affected because of the deficit of hilar mossy cells. Moreover, analysis of Rac function in hippocampal cultures shows that spine formation is strongly hampered only in neurons lacking both Rac proteins. These findings show for the first time that both Rac1 and Rac3 are important for the development of the nervous system, wherein they play complementary roles during late stages of neuronal and brain development.-Corbetta, S., Gualdoni, S., Ciceri, G., Monari, M., Zuccaro, E., Tybulewicz, V. L. J., de Curtis, I. Essential role of Rac1 and Rac3 GTPases in neuronal development. FASEB J. 23, 1347-1357 (2009)