cAMP-induced expression of neuropilin1 promotes retinal axon crossing in the zebrafish optic chiasm.

Growing axons navigate a complex environment as they respond to attractive and repellent guidance cues. Axons can modulate their responses to cues through a G-protein-coupled, cAMP-dependent signaling pathway. To examine the role of G-protein signaling in axon guidance in vivo, we used the GAL4/UAS system to drive expression of dominant-negative heterotrimeric G-proteins (DNG) in retinal ganglion cells (RGCs) of embryonic zebrafish.

The calmodulin-stimulated adenylate cyclase ADCY8 sets the sensitivity of zebrafish retinal axons to midline repellents and is required for normal midline crossing.

The chemokine SDF1 activates a cAMP-mediated signaling pathway that antagonizes retinal responses to the midline repellent slit. We show that knocking down the calmodulin-activated adenylate cyclase ADCY8 makes retinal axons insensitive to SDF1. Experiments in vivo using male and female zebrafish (Danio rerio) confirm a mutual antagonism between slit signaling and ADCY8-mediated signaling.