Linking cell fate, trajectory choice, and target selection: genetic analysis of Sema-2b in olfactory axon targeting

Neuron. 2013 May 22;78(4):673-86. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Axons / physiology*
  • Drosophila
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Gene Expression Regulation, Developmental
  • Growth Cones / physiology
  • 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


  • Drosophila Proteins
  • Protein Sorting Signals
  • Semaphorins