Investigations of signaling pathways in axon growth and guidance

The retinotectal projection in chick is a well studied model system for axon guidance. The 'stripe assay' provides a unique tool for investigating underlying molecules and mechanisms of axon guidance by non-diffusible substrate bound molecules in vitro. By combining this assay with a modified 'Campenot chamber', we have now investigated the role of several second messenger systems in this type of axon guidance by confronting growing axons with various drugs that are known to influence intracellular signaling. We have shown that extracellular, and most probably intracellular Ca++ is not required for this type of axon guidance, which also rules out the need for Ca++-dependent adhesion molecules like cadherins. While at least calmodulin and protein kinase C seem to be involved in axon elongation, inhibiting their function did not alter the growth cones' choice. Inhibition of other kinases, G-proteins and signaling components also failed to influence this guidance. These results may indicate that parallel signaling pathways take part in the molecular mechanism of this type of axon guidance.