Distinct roles of Rac1/Cdc42 and Rho/Rock for axon outgrowth and nucleokinesis of precerebellar neurons toward netrin 1
Distinct roles of Rac1/Cdc42 and Rho/Rock for axon outgrowth and nucleokinesis of precerebellar neurons toward netrin 1
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DOI：
10.1242/dev.01162
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发表时间：
2004-06-01
期刊：
影响因子：
4.6
通讯作者：
Bloch-Gallego, E
中科院分区：
文献类型：
--
作者：
Causeret, F;Hidalgo-Sanchez, M;Bloch-Gallego, E
在胚胎发育过程中，切向迁移的小脑前神经元发出一个前导过程，然后将它们的核移位到前导过程中（核分裂）。Netrin 1（也称为netrin-1）在体内和体外都作为小脑前神经元（PCN）的亲神经性迁移的化学引诱因子。在目前的工作中，我们分析了Rho GTP酶，可以直接轴突生长和/或核迁移。我们发现，Rho GTPases在发展中的PCN的表达模式是一致的，他们参与的PCN从菱形唇的迁移。我们报告说，药理学抑制Rho增强轴突生长的PCN，并防止细胞核迁移向netrin 1源，而抑制Rac和Cdc 42亚家族损害轴突生长的PCN，而不影响迁移。我们表明，通过药理学抑制，Rho信号通过Rock激活指导嗜神经细胞迁移。总之，我们的研究结果表明，Rho/Rock作用于有利于PCN切向迁移过程中核转位的信号通路。因此，响应于netrin 1的PCN的轴突延伸和核迁移不是严格依赖的过程，因为：（1）涉及不同的小GTP酶;（2）当迁移被阻断时可以发生轴突延伸;以及（3）当轴突生长受损时可以发生迁移。
During embryonic development, tangentially migrating precerebellar neurons emit a leading process and then translocate their nuclei inside it (nucleokinesis). Netrin 1 (also known as netrin-1) acts as a chemoattractant factor for neurophilic migration of precerebellar neurons (PCN) both in vivo and in vitro. In the present work, we analyzed Rho GTPases that could direct axon outgrowth and/or nuclear migration. We show that the expression pattern of Rho GTPases in developing PCN is consistent with their involvement in the migration of PCN from the rhombic lips. We report that pharmacological inhibition of Rho enhances axon outgrowth of PCN and prevents nuclei migration toward a netrin 1 source, whereas inhibition of Rac and Cdc42 sub-families impair neurite outgrowth of PCN without affecting migration. We show, through pharmacological inhibition, that Rho signaling directs neurophilic migration through Rock activation. Altogether, our results indicate that Rho/Rock acts on signaling pathways favoring nuclear translocation during tangential migration of PCN. Thus, axon extension and nuclear migration of PCN in response to netrin 1 are not strictly dependent processes because: (1) distinct small GTPases are involved; (2) axon extension can occur when migration is blocked; and (3) migration can occur when axon outgrowth is impaired.