Effects of pharmacological inhibition of small GTPases on axon extension and migration of enteric neural crest-derived cells.
In the developing enteric nervous system, there is a close association between migrating neural crest-derived cells and the axons of early differentiating neurons. We used pharmacological inhibitors of small GTPases to determine if crest cell migration and axon growth could be uncoupled in cultured intact explants of embryonic mouse gut and slices of embryonic gut grown on collagen gels containing GDNF. Inhibition of the Rho effectors, ROCKI/II, or Rac/Cdc42 inhibited both cell migration and neurite growth in intact explants of embryonic gut. The effects of both ROCKI/II and Rac/Cdc42 inhibitors were more severe on cell migration and axon extension in gut explants from Ret(+/-) mice than in explants from wildtype mice, indicating that Rho GTPases probably act downstream of the receptor tyrosine kinase, Ret. Inhibition of ROCKI/II had different effects on migration and axon extension in gut slices grown on collagen gels containing GDNF from that seen in intact explants of gut. We conclude that ROCKI/II and Rac/Cdc42 are required for both neural crest-derived cell migration and axon growth in the developing gut.
Stewart
Ashley L
AL
Department of Anatomy and Cell Biology, University of Melbourne, 3010, VIC, Australia.
Young
Heather M
HM
Popoff
Michel
M
Anderson
Richard B
RB
D000818:Animals; D001369:Axons / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004622:Embryo, Mammalian; D017615:Enteric Nervous System / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007422:Intestines; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D051379:Mice; D020559:Monomeric GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D009432:Neural Crest / Q000166:cytology; D009474:Neurons; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D020764:cdc42 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000502:physiology*; D020744:rac GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D054460:rho-Associated Kinases
D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020559:Monomeric GTP-Binding Proteins; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins