Linking Cell Fate, Trajectory Choice, and Target Selection: Genetic Analysis of Sema-2b in Olfactory Axon Targeting

• Published in: Neuron (Cambridge, Mass.) Mass.), 2013-05, Vol.78 (4), p.673-686
• Main Authors: Joo, William J., Sweeney, Lora B., Liang, Liang, Luo, Liqun
• Format: Article
• Language: English
• Subjects: Animals; Animals, Genetically Modified; Axons - physiology; Drosophila; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Gene Expression Regulation, Developmental; Growth Cones - physiology; Medical research; Neuropil - cytology; Neuropil - metabolism; Olfactory Bulb - cytology; Olfactory Bulb - metabolism; Olfactory Pathways - cytology; Olfactory Receptor Neurons - growth & development; Olfactory Receptor Neurons - metabolism; Protein Sorting Signals; Semaphorins - genetics; Semaphorins - metabolism
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2013.03.022

Neural circuit assembly requires selection of specific cell fates, axonal trajectories, and synaptic targets. By analyzing the function of a secreted semaphorin, Sema-2b, in Drosophila olfactory receptor neuron (ORN) development, we identified multiple molecular and cellular mechanisms that link these events. Notch signaling limits Sema-2b expression to ventromedial ORN classes, within which Sema-2b cell-autonomously sensitizes ORN axons to external semaphorins. Central-brain-derived Sema-2a and Sema-2b attract Sema-2b-expressing axons to the ventromedial trajectory. In addition, Sema-2b/PlexB-mediated axon-axon interactions consolidate this trajectory choice and promote ventromedial axon-bundle formation. Selecting the correct developmental trajectory is ultimately essential for proper target choice. These findings demonstrate that Sema-2b couples ORN axon guidance to postsynaptic target neuron dendrite patterning well before the final target selection phase, and exemplify how a single guidance molecule can drive consecutive stages of neural circuit assembly with the help of sophisticated spatial and temporal regulation. •Notch signaling represses Sema-2b expression in specific ORNs•Axonal Sema-2b acts cell-autonomously to sensitize ORN axons to external semaphorins•Central brain semaphorins and axon-axon interactions direct trajectory choice•Early axon trajectory choice constrains final glomerular target selection Joo et al. find that Notch signaling represses secreted Sema-2b to control a binary trajectory choice in olfactory axons, and that Sema-2b acts both cell-autonomously and nonautonomously to connect multiple phases of olfactory circuit wiring.