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

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Abstract
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+] 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. © 1997 John Wiley & Sons, Inc. J Neurobiol 33: 825–834, 1997