Distinct roles of Rac1/Cdc42 and Rho/Rock for axon outgrowth and nucleokinesis of precerebellar neurons toward netrin 1

被引:73
作者
Causeret, F
Hidalgo-Sanchez, M
Fort, P
Backer, S
Popoff, MR
Gauthier-Rouvière, C
Bloch-Gallego, E
机构
[1] Univ Paris 05, Inst Cochin, CNRS 8104, INSERM U567,CHU Cochin,GDPM, F-75014 Paris, France
[2] CNRS, CRBM, FRE2593, F-34293 Montpellier, France
[3] Inst Pasteur, Unite Bacteries Anaerobies & Toxines, F-75724 Paris 15, France
来源
DEVELOPMENT | 2004年 / 131卷 / 12期
关键词
nuclear translocation; hindbrain; chemotropic molecules; Rho GTPases; mice; collagen assays; in situ hybridization; GST-RBD-Rhotekin;
D O I
10.1242/dev.01162
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:2841 / 2852
页数:12
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