Semaphorin 2b Regulates Sleep-Circuit Formation in the Drosophila Central Brain

The fan-shaped body (FB) neuropil in the Drosophila brain central complex (CX) controls a variety of adult behaviors, including navigation and sleep. How neuronal processes are organized into precise layers and columns in the FB and how alterations in FB neural-circuit wiring affect animal behaviors are unknown. We report here that secreted semaphorin 2b (Sema-2b) acts through its transmembrane receptor Plexin B (PlexB) to locally attract neural processes to specific FB laminae. Aberrant Sema-2b/PlexB signaling leads to select disruptions in neural lamination, and these disruptions result in the formation of ectopic inhibitory connections between subsets of FB neurons. These structural alternations and connectivity defects are associated with changes in fly sleep and arousal, emphasizing the importance of lamination-mediated neural wiring in a central brain region critical for normal sleep behavior.