[K4]: Synapse formation: Coordinating pre‐ and postsynaptic differentiation at the neuromuscular junction

Preand postsynaptic partners organize each other’s differentiation during the formation of chemical synapses. The axon presents factors that organize postsynaptic differentiation, the target presents factors that organize presynaptic differentiation, and both cells express genes that bias synaptogenesis in favor of specific partners. Together, these factors lead to perfect apposition of appropriate preand postsynaptic specializations. We are analyzing these interactions at the skeletal neuromuscular junction. Genetic studies in vivo andmolecular analysis invitro have led to identification of candidate anterograde (agrin and acetylcholine) and retrograde (laminins, collagens, and FGFs) organizers as well as some of their receptors and signal transduction components. I will describe recent progress toward defining rudimentary genetic pathways for preand postsynaptic differentiation. Genetics can only show that these proteins play a role, however, not what the role is. The latter requires in vivo imaging, in our case using animals that express GFP and its spectral variants in defined cellular populations. By watching synapses as they form in wild-type andmutant animals, we can assess the cellular consequences of defined molecular perturbations.