Distinct roles of Rac1/Cdc42 and Rho/Rock for axon outgrowth and nucleokinesis of precerebellar neurons toward netrin 1.
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.
Causeret
Frédéric
F
Institut Cochin, GDPM, INSERM U567, CNRS 8104, Université Paris V, CHU Cochin, 24 rue du Faubourg Saint Jacques, 75014 Paris, France.
Hidalgo-Sanchez
Matias
M
Fort
Philippe
P
Backer
Stéphanie
S
Popoff
Michel-Robert
MR
Gauthier-Rouvière
Cécile
C
Bloch-Gallego
Evelyne
E
D000818:Animals; D001369:Axons / Q000502:physiology*; D002465:Cell Movement; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D002531:Cerebellum / Q000166:cytology / Q000196:embryology*; D005314:Embryonic and Fetal Development / Q000502:physiology*; D051379:Mice; D009414:Nerve Growth Factors / Q000502:physiology*; D000075388:Netrin-1; D009474:Neurons / Q000166:cytology*; D012234:Rho Factor / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; D012234:Rho Factor; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein