Adenylate Cyclase 1 modulates peripheral nerve branching patterns.

The Ca(2+)-stimulated adenylate cyclase 1 (AC1) is a key mediator of retinotopic map refinement and is required for the retraction response of retinal growth cones to the guidance cue ephrin-A5. We show here that AC1 is dynamically expressed in subpopulations of motor neurons in the spinal cord and sensory neurons of the dorsal root ganglia during development. AC1 was first detected around E12.5 in motoneurons of the medial aspect of the lateral motor column (LMCm) and the lateral region of the medial motor column (MMCl), which project to the ventral limb and body wall musculature, respectively. Expression levels gradually increased until they reached a maximum at a time when peripheral sensory and motor axons branch and establish connections with their targets. In barrelless mice, where a mutation inactivates the AC1 gene, sensory projections to the skin in the limbs and trunk region as well as innervations of the intercostal musculature provided by MMCl axons show increased branching. These results suggest a function of AC1 in the formation of peripheral nerve trajectories such as branching and pruning, after the initial projections have been laid down.