title: Secreted semaphorins from degenerating larval ORN axons direct adult projection neuron dendrite targeting.
abstract: During assembly of the Drosophila olfactory circuit, projection neuron (PN) dendrites prepattern the developing antennal lobe before the arrival of axons from their presynaptic partners, the adult olfactory receptor neurons (ORNs). We previously found that levels of transmembrane Semaphorin-1a, which acts as a receptor, instruct PN dendrite targeting along the dorsolateral-ventromedial axis. Here we show that two secreted semaphorins, Sema-2a and Sema-2b, provide spatial cues for PN dendrite targeting. Sema-2a and Sema-2b proteins are distributed in gradients opposing the Sema-1a protein gradient, and Sema-1a binds to Sema-2a-expressing cells. In Sema-2a and Sema-2b double mutants, PN dendrites that normally target dorsolaterally in the antennal lobe mistarget ventromedially, phenocopying cell-autonomous Sema-1a removal from these PNs. Cell ablation, cell-specific knockdown, and rescue experiments indicate that secreted semaphorins from degenerating larval ORN axons direct dendrite targeting. Thus, a degenerating brain structure instructs the wiring of a developing circuit through the repulsive action of secreted semaphorins.
authors.affiliation: Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
authors.forename: Lora B
authors.initials: LB
authors.lastname: Sweeney
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Chou
authors.forename: Zhuhao
authors.initials: Z
authors.lastname: Wu
authors.forename: William
authors.initials: W
authors.lastname: Joo
authors.forename: Takaki
authors.initials: T
authors.lastname: Komiyama
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Potter
authors.forename: Alex L
authors.initials: AL
authors.lastname: Kolodkin
authors.forename: K Christopher
authors.initials: KC
authors.lastname: Garcia
authors.forename: Liqun
authors.initials: L
authors.lastname: Luo
mesh_terms: D055011:Ablation Techniques / Q000379:methods; D000367:Age Factors; D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology*; D003712:Dendrites / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D007814:Larva; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009833:Olfactory Pathways / Q000166:cytology* / Q000254:growth & development; D018034:Olfactory Receptor Neurons / Q000166:cytology*; D011485:Protein Binding; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D039961:Semaphorins