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Tyrosine kinase inhibition produces specific alterations in axon guidance in the grasshopper embryo

Menon, Kaushiki P. and Zinn, Kai (1998) Tyrosine kinase inhibition produces specific alterations in axon guidance in the grasshopper embryo. Development, 125 (20). pp. 4121-4131. ISSN 0950-1991.

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Tyrosine kinase signaling pathways are essential for process outgrowth and guidance during nervous system development. We have examined the roles of tyrosine kinase activity in programming growth cone guidance decisions in an intact nervous system in which neurons can be individually identified. We applied the tyrosine kinase inhibitors herbimycin A and genistein to whole 40% grasshopper embryos placed in medium, or injected the inhibitors into intact grasshopper eggs. Both inhibitors caused interneuronal axons that normally would grow along the longitudinal connectives to instead leave the central nervous system (CNS) within the segmental nerve root and grow out toward the body wall muscles. In addition, herbimycin A produced pathfinding errors in which many longitudinal axons crossed the CNS midline. To study how this drug affected guidance decisions made by individual growth cones, we dye-filled the pCC interneuron, which normally extends an axon anteriorly along the ipsilateral longitudinal connective. In the presence of herbimycin A, the pCC growth cone was redirected across the anterior commissure. These phenotypes suggest that tyrosine kinase inhibition blocks a signaling mechanism that repels the growth cones of longitudinal connective neurons and prevents them from crossing the midline.

Item Type:Article
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URLURL TypeDescription
Menon, Kaushiki P.0000-0003-1039-4704
Zinn, Kai0000-0002-6706-5605
Additional Information:Copyright © 1998 by Company of Biologists. Accepted 24 July; published on WWW 14 September 1998. We thank Michael Bastiani, Hugo Bellen and Mark Perin for antibodies; Barry Condron, Haig Keshishian, Chand Desai, Qi Sun and Richard Baines for helpful discussions; Doris Koo for help with in vivo microinjections; Rosalind Young for advice on EM techniques; Anna Vlasek for advice on western blots and Gilles Laurent for the use of his grasshopper colony. We also thank Markus Friedrich, Benno Schindelholz and Rusty Lansford for comments on the manuscript. This work was supported by an NIH RO1 grant and a Human Frontiers Science Project grant to K. Z.; K. M. was supported by an NRSA postdoctoral fellowship.
Funding AgencyGrant Number
Human Frontier Science ProgramUNSPECIFIED
Subject Keywords:Tyrosine kinase; Grasshopper; Midline; Neural development; Growth cone
Issue or Number:20
Record Number:CaltechAUTHORS:20090918-135908333
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Official Citation:KP Menon, and K Zinn Tyrosine kinase inhibition produces specific alterations in axon guidance in the grasshopper embryo Development 125: 4121-4131.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:15984
Deposited By: George Porter
Deposited On:22 Sep 2009 18:32
Last Modified:09 Mar 2020 13:19

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