title: Requirement for Slit-1 and Robo-2 in zonal segregation of olfactory sensory neuron axons in the main olfactory bulb.
abstract: The formation of precise stereotypic connections in sensory systems is critical for the ability to detect and process signals from the environment. In the olfactory system, olfactory sensory neurons (OSNs) project axons to spatially defined glomeruli within the olfactory bulb (OB). A spatial relationship exists between the location of OSNs within the olfactory epithelium (OE) and their glomerular targets along the dorsoventral axis in the OB. The molecular mechanisms underlying the zonal segregation of OSN axons along the dorsoventral axis of the OB are poorly understood. Using robo-2(-/-) (roundabout) and slit-1(-/-) mice, we examined the role of the Slit family of axon guidance cues in the targeting of OSN axons during development. We show that a subset of OSN axons that normally project to the dorsal region of the OB mistarget and form glomeruli in the ventral region in robo-2(-/-) and slit-1(-/-) mice. In addition, we show that the Slit receptor, Robo-2, is expressed in OSNs in a high dorsomedial to low ventrolateral gradient across the OE and that Slit-1 and Slit-3 are expressed in the ventral region of the OB. These results indicate that the dorsal-to-ventral segregation of OSN axons are not solely defined by the location of OSNs within the OE but also relies on axon guidance cues.
authors: Montreal Neurological Institute, Centre for Neuronal Survival, Montréal, Québec, Canada H3A 2B4.
authors: Jin Hyung
authors: JH
authors: Cho
authors: Manon
authors: M
authors: Lépine
authors: William
authors: W
authors: Andrews
authors: John
authors: J
authors: Parnavelas
authors: Jean-François
authors: JF
authors: Cloutier
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D004622:Embryo, Mammalian; D005260:Female; D015870:Gene Expression / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D017403:In Situ Hybridization / Q000379:methods; D008565:Membrane Proteins / Q000172:deficiency / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D016660:NAD(P)H Dehydrogenase (Quinone); D009252:NADPH Dehydrogenase / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000502:physiology*; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D009475:Neurons, Afferent / Q000166:cytology*; D009830:Olfactory Bulb / Q000166:cytology*; D011247:Pregnancy; D011971:Receptors, Immunologic / Q000172:deficiency / Q000378:metabolism*; D000097905:Roundabout Proteins
chemical_list: D008565:Membrane Proteins; D016660:NAD(P)H Dehydrogenase (Quinone); D009252:NADPH Dehydrogenase; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D011971:Receptors, Immunologic; C108768:Ncam2 protein, mouse; C498888:Robo2 protein, mouse; D000097905:Roundabout Proteins; C120010:Slit1 protein, mouse; C432251:Slit3 protein, mouse; C491732:Nqo1 protein, mouse
references: Cell. 1999 Mar 19;96(6):795-806
references: 10102268
references: J Neurosci. 1999 Jun 1;19(11):4428-36
references: 10341244
references: Dev Biol. 1999 Aug 15;212(2):290-306
references: 10433822
references: J Neurosci. 1999 Oct 1;19(19):8409-18
references: 10493742
references: Cell Mol Biol (Noisy-le-grand). 1999 Sep;45(6):763-79
references: 10541474
references: Neuron. 2000 Apr;26(1):81-91
references: 10798394
references: J Neurosci. 2000 Oct 15;20(20):7691-7
references: 11027230
references: Neuron. 2000 Nov;28(2):437-47
references: 11144354
references: Mol Cell Neurosci. 2001 May;17(5):872-82
references: 11358484
references: J Comp Neurol. 2001 Jul 30;436(3):351-62
references: 11438935
references: Mol Cell Neurosci. 2001 Sep;18(3):283-95
references: 11591129
references: Nature. 2001 Nov 8;414(6860):173-9
references: 11700549
references: J Comp Neurol. 2002 Jan 7;442(2):130-55
references: 11754167
references: Neuron. 2002 Jan 17;33(2):219-32
references: 11804570
references: Neuron. 2002 Mar 14;33(6):877-92
references: 11906695
references: J Neurosci. 2002 May 15;22(10):4025-35
references: 12019322
references: J Neurosci. 2002 Jun 1;22(11):4499-508
references: 12040057
references: Mol Cell Neurosci. 2002 Dec;21(4):534-45
references: 12504588
references: Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5217-22
references: 12702769
references: Cell. 2003 Aug 8;114(3):311-22
references: 12914696
references: J Neurosci. 2004 Jan 14;24(2):356-69
references: 14724234
references: Neuroreport. 1992 Dec;3(12):1053-6
references: 1493216
references: Development. 2004 May;131(9):1903-12
references: 15056612
references: Eur J Neurosci. 2004 Apr;19(7):1800-10
references: 15078553
references: Eur J Neurosci. 2004 May;19(9):2511-8
references: 15128404
references: Dev Cell. 2004 May;6(5):709-17
references: 15130495
references: Science. 2004 Jun 25;304(5679):1976-9
references: 15178749
references: Cell. 2004 Jun 11;117(6):817-31
references: 15186781
references: Cell. 2004 Jun 11;117(6):833-46
references: 15186782
references: J Neurosci. 2004 Oct 13;24(41):9087-96
references: 15483127
references: Development. 2005 Mar;132(6):1283-93
references: 15716341
references: J Neurosci. 2005 Apr 6;25(14):3586-92
references: 15814789
references: Science. 2006 Oct 27;314(5799):657-61
references: 16990513
references: Cell. 2006 Dec 1;127(5):1057-69
references: 17129788
references: Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):1039-44
references: 17215378
references: Am J Hum Genet. 2007 Apr;80(4):616-32
references: 17357069
references: Development. 2007 Jul;134(13):2481-9
references: 17537788
references: J Neurosci. 2007 Jun 20;27(25):6675-83
references: 17581954
references: Brain Res Bull. 1986 Apr;16(4):445-54
references: 3719376
references: Brain Res Bull. 1986 Apr;16(4):455-62
references: 3719377
references: Cell. 1994 Dec 30;79(7):1245-55
references: 7528109
references: Cell. 1993 May 7;73(3):597-609
references: 7683976
references: Biochim Biophys Acta. 1995 Apr 4;1261(2):249-56
references: 7711068
references: Cell Tissue Res. 1994 Oct;278(1):11-20
references: 7954694
references: Cell. 1994 Dec 16;79(6):981-91
references: 8001145
references: J Biol Chem. 1993 Dec 15;268(35):26494-502
references: 8253778
references: Cell. 1993 Jul 30;74(2):309-18
references: 8343958
references: Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):884-8
references: 8570653
references: Cell. 1996 Nov 15;87(4):675-86
references: 8929536
references: J Neurosci. 1997 Aug 1;17(15):5830-42
references: 9221781
references: J Biol Chem. 1997 Oct 17;272(42):26083-6
references: 9334170
references: Cell. 1998 Apr 3;93(1):47-60
references: 9546391