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

Tyrosine kinase signaling pathways are essential for process outgrowth and guidance during nervous system development, We have examined the roles of t yrosine 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 i ntact grasshopper eggs, Both inhibitors caused interneuronal axons that nor mally would grow along the longitudinal connectives to instead leave the ce ntral nervous system (CNS) within the segmental nerve root and grow out tow ard the body wall muscles. In addition, herbimycin A produced pathfinding e rrors in which many longitudinal axons crossed the CNS midline. To study ho w 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 herbimyci n A, the pCC growth cone was redirected across the anterior commissure, The se phenotypes suggest that tyrosine kinase inhibition blocks a signaling me chanism that repels the growth cones of longitudinal connective neurons and prevents them from crossing the midline.