title: Attractant and repellent cues cooperate in guiding a subset of olfactory sensory axons to a well-defined protoglomerular target.
abstract: Olfactory sensory axons target well-defined intermediate targets in the zebrafish olfactory bulb called protoglomeruli well before they form odorant receptor-specific glomeruli. A subset of olfactory sensory neurons are labeled by expression of the or111-7:IRES:GAL4 transgene whose axons terminate in the central zone (CZ) protoglomerulus. Previous work has shown that some of these axons misproject to the more dorsal and anterior dorsal zone (DZ) protoglomerulus in the absence of Netrin 1/Dcc signaling. In search of additional cues that guide these axons to the CZ, we found that Semaphorin 3D (Sema3D) is expressed in the anterior bulb and acts as a repellent that pushes them towards the CZ. Further analysis indicates that Sema3D signaling is mediated through Nrp1a, while Nrp2b also promotes CZ targeting but in a Sema3D-independent manner. nrp1a, nrp2b and dcc transcripts are detected in or111-7 transgene-expressing neurons early in development and both Nrp1a and Dcc act cell-autonomously in sensory neurons to promote accurate targeting to the CZ. dcc and nrp1a double mutants have significantly more DZ misprojections than either single mutant, suggesting that the two signaling systems act independently and in parallel to direct a specific subset of sensory axons to their initial protoglomerular target.
authors.affiliation: Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Alemji A
authors.initials: AA
authors.lastname: Taku
authors.affiliation: Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Marcaccio
authors.affiliation: Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Wenda
authors.initials: W
authors.lastname: Ye
authors.affiliation: Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Krause
authors.affiliation: Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA raperj@mail.med.upenn.edu.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Raper
mesh_terms: D000818:Animals; D003463:Cues; D000075389:DCC Receptor; D004268:DNA-Binding Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D000075388:Netrin-1; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism*; D039943:Neuropilin-2 / Q000235:genetics / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology* / Q000254:growth & development; D009833:Olfactory Pathways / Q000196:embryology* / Q000502:physiology; D018034:Olfactory Receptor Neurons / Q000166:cytology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D039961:Semaphorins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000075389:DCC Receptor; D004268:DNA-Binding Proteins; C542436:Gal4 protein, zebrafish; D009414:Nerve Growth Factors; D039943:Neuropilin-2; D011956:Receptors, Cell Surface; D039961:Semaphorins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D029961:Zebrafish Proteins; C506552:dcc protein, zebrafish; D039942:Neuropilin-1; D000075388:Netrin-1
keywords: Axon guidance; Olfactory development; Protoglomeruli; Sema3D; Semaphorin; Zebrafish