Guidance of CNS growth cones by substratum grooves and ridges: Effects of inhibitors of the cytoskeleton, calcium channels and signal transduction pathways

Ann M. Rajnicek*, Colin D. McCaig

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

158 Citations (Scopus)

Abstract

We exploited our observation that embryonic Xenopus spinal neurites align parallel to grooves in a quartz surface and that embryonic rat hippocampal neurites align perpendicular to shallow, narrow grooves to investigate the mechanism of growth cone contact guidance. Substratum topography affected the pattern of growth cone filopodia and microtubules but parallel orientation of Xenopus neurites and perpendicular orientation of hippocampal neurites were unperturbed by cytochalasin B, which virtually eliminated filopodia. Hippocampal growth cone orientation and turning in response to grooves was unaffected by disruption of microtubules using taxol or nocodazole. Gross cytoskeletal reorganization on grooved substrata was therefore not required for growth cone steering. Inhibitors were used to identify the signal transduction pathway for perpendicular alignment of hippocampal neurites. Alignment persisted in the presence of gadolinium chloride, a blocker of stretch-activated calcium channels, the G protein inhibitor pertussis toxin, the protein tyrosine kinase inhibitor genistein, the protein kinase A and G inhibitor HA1004, the protein kinase A inhibitor KT5720 and the protein kinase G inhibitor KT5823. Low concentrations of the protein kinase C inhibitors staurosporine, bisindolylmaleimide or H-7 did not affect perpendicular orientation but higher concentrations inhibited it. The calcium channel blockers flunarizine, nifedipine and diltiazem also inhibited perpendicular orientation. Influx of calcium and protein kinase C activity therefore appear to be involved in perpendicular contact guidance.

Original languageEnglish
Pages (from-to)2915-2924
Number of pages10
JournalJournal of Cell Science
Volume110
Issue number23
Publication statusPublished - 1 Dec 1997

Keywords

  • Contact guidance
  • Filopodium
  • Growth cone
  • Hippocampal neuron
  • Microtubule
  • Xenopus neuron

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