Retinal axon growth cone responses to different environmental cues are mediated by different second-messenger systems

J Neurobiol. 1997 Nov 20;33(6):825-34. doi: 10.1002/(sici)1097-4695(19971120)33:6<825::aid-neu9>;2-b.


Numerous studies have shown that the developing tip of a neurite, the growth cone, can respond to environmental cues with behaviors such as guidance or collapse. To assess whether a given cell type can use more than one second-messenger pathway for a single behavior, we compared the influence of two well-characterized guidance cues on growth cones of chick temporal retinal ganglion cells. The first cue was the repulsive activity derived from the posterior optic tectum (p-membranes), and the second was the collapse-inducing activity derived from oligodendrocytes known as NI35/NI250. p-Membranes caused permanent growth cone collapse with no recovery after several hours, while NI35 caused transient collapse followed by recovery after about 10 min. The p-membrane-induced collapse was found to be Ca2+ independent, as shown using the Ca2+-sensitive dye Fura-2 and by the persistence of collapse in Ca2+-free medium. Dantrolene, a blocker of the ryanodine receptor, had only a minor effect on the collapse frequency caused by p-membranes. In contrast, the NI35-induced collapse was clearly Ca2+ dependent. [Ca2+]i increased sevenfold preceding collapse, and both dantrolene and antibodies against NI35 significantly reduced both the Ca2+ increase and the collapse frequency. Thus, even in a single cell type, growth cone collapse induced by two different signals can be mediated by two different second-messenger systems.

MeSH terms

  • Animals
  • Axonal Transport / physiology*
  • Calcium / metabolism
  • Chick Embryo
  • Dantrolene / pharmacology
  • Fura-2
  • GAP-43 Protein / metabolism
  • Glycoproteins / metabolism
  • Ionophores
  • Myelin Proteins / metabolism
  • Rats
  • Retinal Ganglion Cells / physiology*
  • Ryanodine Receptor Calcium Release Channel / drug effects
  • Ryanodine Receptor Calcium Release Channel / metabolism
  • Second Messenger Systems / physiology*
  • Semaphorin-3A


  • GAP-43 Protein
  • Glycoproteins
  • Ionophores
  • Myelin Proteins
  • Ryanodine Receptor Calcium Release Channel
  • Semaphorin-3A
  • Dantrolene
  • Calcium
  • Fura-2