Elsevier

Developmental Biology

Volume 307, Issue 1, 1 July 2007, Pages 92-104
Developmental Biology

Effects of pharmacological inhibition of small GTPases on axon extension and migration of enteric neural crest-derived cells

https://doi.org/10.1016/j.ydbio.2007.04.024Get rights and content
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Abstract

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.

Keywords

Rho
ROCK
Rac
Cdc42
GDNF
Ret
Axon guidance

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