title: Robo2 is required for establishment of a precise glomerular map in the zebrafish olfactory system.
abstract: Olfactory sensory neurons (OSNs) expressing a given odorant receptor project their axons to specific glomeruli, creating a topographic odor map in the olfactory bulb (OB). The mechanisms underlying axonal pathfinding of OSNs to their precise targets are not fully understood. Here, we demonstrate that Robo2/Slit signaling functions to guide nascent olfactory axons to the OB primordium in zebrafish. robo2 is transiently expressed in the olfactory placode during the initial phase of olfactory axon pathfinding. In the robo2 mutant, astray (ast), early growing olfactory axons misroute ventromedially or posteriorly, and often penetrate into the diencephalon without reaching the OB primordium. Four zebrafish Slit homologs are expressed in regions adjacent to the olfactory axon trajectory, consistent with their role as repulsive ligands for Robo2. Masking of endogenous Slit gradients by ubiquitous misexpression of Slit2 in transgenic fish causes posterior pathfinding errors that resemble the ast phenotype. We also found that the spatial arrangement of glomeruli in OB is perturbed in ast adults, suggesting an essential role for the initial olfactory axon scaffold in determining a topographic glomerular map. These data provide functional evidence for Robo2/Slit signaling in the establishment of olfactory neural circuitry in zebrafish.
authors.affiliation: Laboratory for Neurobiology of Synapse, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Miyasaka
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sato
authors.forename: Sang-Yeob
authors.initials: SY
authors.lastname: Yeo
authors.forename: Lara D
authors.initials: LD
authors.lastname: Hutson
authors.forename: Chi-Bin
authors.initials: CB
authors.lastname: Chien
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okamoto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yoshihara
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009833:Olfactory Pathways / Q000196:embryology* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism; D029961:Zebrafish Proteins; D000097905:Roundabout Proteins
chemical_list: D006023:Glycoproteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D029961:Zebrafish Proteins; C498889:robo2 protein, zebrafish; D000097905:Roundabout Proteins; C120566:slit protein, vertebrate