Recent advances in inter-cellular interactions during neural circuit assembly.

Neural circuit assembly is regulated by inter-cellular interactions involving secreted and surface-tethered guidance molecules. Here, we review recent progress in our understanding of their mechanisms-of-action and biological effects. We discuss mechanisms through which the secreted cue Netrin-1 regulates neuron migration and highlight novel roles for axon-derived secreted guidance cues. We cover recent structural work at atomic resolution that provides new insights into the activation mechanisms of axon guidance receptors and into protein complexes containing cell adhesion molecules, such as Teneurin (Ten), Latrophilin (Lphn) and FLRT. Ten-Ten homophilic, Ten-Lphn heterophilic, and Ten-Lphn-FLRT tripartite complexes seem to elicit distinct context-dependent cellular responses. Seemingly opposite responses can also be triggered by the Eph/ephrin signaling system. Here, recent work provides a simple mechanism for the decision of forming a new synapse versus rejection of the pre-synaptic partner. These studies identify novel regulatory mechanisms and biological functions that will apply generally in developing neural systems.