title: Netrin/DCC signaling guides olfactory sensory axons to their correct location in the olfactory bulb.
abstract: Olfactory sensory neurons expressing particular olfactory receptors project to specific reproducible locations within the bulb. The axonal guidance cues that organize this precise projection pattern are only beginning to be identified. To aid in their identification and characterization, we generated a transgenic zebrafish line, OR111-7:IRES:Gal4, in which a small subset of olfactory sensory neurons is labeled. Most sensory neurons expressing the OR111-7 transgene project to a specific location within the bulb, the central zone protoglomerulus, while a smaller number project to the lateral glomerulus 1 protoglomerulus. Inhibiting Netrin/DCC (deleted in colorectal cancer) signaling perturbs the ability of OR111-7-expressing axons to enter the olfactory bulb and alters their patterns of termination within the bulb. The Netrin receptor DCC is expressed in olfactory sensory neurons around the time that they elaborate their axons, netrin1a is expressed near the medial-most margin of the olfactory bulb, and netrin1b is expressed within the ventral region of the bulb. Loss of Netrin/DCC signaling components causes some OR111-7-expressing sensory axons to wander posteriorly after exiting the olfactory pit, away from netrin-expressing areas in the bulb. OR111-7-expressing axons that enter the bulb target the central zone less precisely than normal, spreading away from netrin-expressing regions. These pathfinding errors can be corrected by the reexpression of DCC within OR111-7 transgene-expressing neurons in DCC morphant embryos. These findings implicate Netrins as the only known attractants for olfactory sensory neurons, first drawing OR111-7-expressing axons into the bulb and then into the ventromedially positioned central zone protoglomerulus.
authors.affiliation: Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Vanisha
authors.initials: V
authors.lastname: Lakhina
authors.forename: Christina L
authors.initials: CL
authors.lastname: Marcaccio
authors.forename: Xin
authors.initials: X
authors.lastname: Shao
authors.forename: Mark E
authors.initials: ME
authors.lastname: Lush
authors.forename: Roshan A
authors.initials: RA
authors.lastname: Jain
authors.forename: Esther
authors.initials: E
authors.lastname: Fujimoto
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Bonkowsky
authors.forename: Michael
authors.initials: M
authors.lastname: Granato
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Raper
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D000075389:DCC Receptor; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008297:Male; D057054:Molecular Imaging / Q000379:methods; D060172:Morpholinos / Q000494:pharmacology; D009154:Mutation; D009414:Nerve Growth Factors / Q000378:metabolism / Q000502:physiology*; D000075388:Netrin-1; D009830:Olfactory Bulb / Q000033:anatomy & histology* / Q000187:drug effects; D051842:Olfactory Marker Protein / Q000235:genetics / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000187:drug effects / Q000502:physiology; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*; D018035:Receptors, Odorant / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology*; D015027:Zebrafish / Q000235:genetics; D029961:Zebrafish Proteins / Q000378:metabolism / Q000502:physiology*
chemical_list: D000075389:DCC Receptor; D060172:Morpholinos; D009414:Nerve Growth Factors; D051842:Olfactory Marker Protein; D011956:Receptors, Cell Surface; D018035:Receptors, Odorant; D050052:TRPC Cation Channels; D025521:Tumor Suppressor Proteins; D029961:Zebrafish Proteins; C506552:dcc protein, zebrafish; D000075388:Netrin-1