Target recognition and synaptogenesis by motor axons: responses to the sidestep protein

Sidestep (Side) is a pivotal molecular player in embryonic motor axon pathfinding. But questions about its functional repertoire remain: (i) can Side permanently overturn targeting preferences? (ii) does it promote synaptogenesis, and (iii) can Side facilitate synaptic stabilization? To address these questions, Side was temporally and spatially misexpressed and the visible consequences for neuromuscular junction morphology were assessed. When Side was misexpressed either broadly or selectively in muscles during targeting in a wildtype background motor axon targeting preferences were permanently overturned. However the misexpression of Side in all muscles post-targeting neither changed synapse morphology, nor compensated for a lack of the synapse-stabilizing protein Fasciclin II (FasII). Rather Side appears to be dependent on FasII, instead of on intrinsic ability, for sustaining targeting changes. We propose that Side helps to bring motor axons to their correct muscle targets and promotes synaptogenesis, then FasII serves to stabilize the synaptic contacts.