Odorant Receptor Gene Choice and Axonal Projection in the Mouse Olfactory System

  • T. Imai
  • H. Sakano
Chapter

Abstract

In the mouse olfactory system, each olfactory sensory neuron (OSN) expresses a single type of odorant receptor (OR) out of approximately 1,000 in a monoallelic manner. Furthermore, OSNs expressing the same OR converge their axons to a specific set of glomeruli on the olfactory bulb. These two basic principles are fundamental to the peripheral olfactory system, and are regulated by the expressed OR protein itself. Singular OR gene choice is ensured by the combination of stochastic enhancer–promoter interaction and negative-feedback regulation by OR proteins. In the axonal projection, OR-derived cyclic AMP signals and neuronal activity determine the expression levels of axon guidance/sorting molecules, and thereby direct glomerular positioning and axon sorting.

References and Recommended Reading

  1. Astic L, Saucier D (1986)Anatomical mapping of the neuroepithelial projection to the olfactory bulb in the rat. Brain Res Bull 16(4):445–454PubMedCrossRefGoogle Scholar
  2. Barnea G, O'Donnell S, Mancia F, Sun X, Nemes A, Mendelsohn M, Axel R(2004)Odorant receptors on axon termini in the brain. Science 304(5676):1468PubMedCrossRefGoogle Scholar
  3. Belluscio L, Gold GH, Nemes A, Axel R (1998)Mice deficient in G(olf) are anosmic.Neuron 20(1):69–81PubMedCrossRefGoogle Scholar
  4. Belluscio L, Lodovichi C, Feinstein P, Mombaerts P, Katz LC (2002)Odorant receptors instruct functional circuitry in the mouse olfactory bulb.Nature 419(6904):296–300PubMedCrossRefGoogle Scholar
  5. Buck L, Axel R (1991)A novel multigene family may ncode odorant receptors: a molecular basis for odor recognition.Cell 65:175–187PubMedCrossRefGoogle Scholar
  6. Chesler AT, Zou DJ, Le Pichon CE, Peterlin ZA, Matthews GA, Pei X, Miller MC, Firestein S (2007)A G protein/cAMP signal cascade is required for axonal convergence into olfactory glomeruli.Proc Natl Acad Sci USA 104(3):1039–1044CrossRefGoogle Scholar
  7. Chess A, Simon I, Cedar H, Axel R (1994)Allelic inactivation regulates olfactory receptor gene expression.Cell 78(5):823–834PubMedCrossRefGoogle Scholar
  8. Cho JH, Lépine M, Andrews W, Parnavelas J, Cloutier JF (2007)Requirement for Slit-1 and Robo-2 in zonal segregation of olfactory sensory neuron axons in the main olfactory bulb.J Neurosci 27(34):9094–9104PubMedCrossRefGoogle Scholar
  9. Col JA, Matsuo T, Storm DR, Rodriguez I (2007)Adenylyl cyclase-dependent axonal targeting in the olfactory system.Development 134(13):2481–2489PubMedCrossRefGoogle Scholar
  10. Conzelmann S, Malun D, Breer H, Strotmann J (2001)Brain targeting and glomerulus formation of two olfactory neuron populations expressing related receptor types.Eur J Neurosci 14(10):1623–1632PubMedCrossRefGoogle Scholar
  11. Cutforth T, Moring L, Mendelsohn M, Nemes A, Shah NM, Kim MM, Frisen J, Axel R (2003)Axonal ephrin-As and odorant receptors: coordinate determination of the olfactory sensory map.Cell 114(3):311–322PubMedCrossRefGoogle Scholar
  12. Eggan K, Baldwin K, Tackett M, Osborne J, Gogos J, Chess A, Axel R, Jaenisch R (2004) Mice cloned from olfactory sensory neurons. Nature 428(6978):44–49PubMedCrossRefGoogle Scholar
  13. Feinstein P, Mombaerts P (2004)A contextual model for axonal sorting into glomeruli in the mouse olfactory system.Cell 117(6):817–831PubMedCrossRefGoogle Scholar
  14. Feinstein P, Bozza T, Rodriguez I, Vassalli A, Mombaerts P (2004) Axon guidance of mouse olfactory sensory neurons by odorant receptors and the beta2 adrenergic receptor.Cell 117(6):833–846PubMedCrossRefGoogle Scholar
  15. Flanagan JG (2006) Neural map specification by gradients.Curr Opin Neurobiol 16(1):59–66CrossRefGoogle Scholar
  16. Fuss SH, Omura M, Mombaerts P (2007) Local and cis effects of the H element on expression of odorant receptor genes in mouse.Cell 130(2):373–384PubMedCrossRefGoogle Scholar
  17. Goodman CS, Shatz CJ (1993)Developmental mechanisms that generate precise patterns of neuronal connectivity.Cell 72(Suppl):77–98PubMedCrossRefGoogle Scholar
  18. Gussing F, Bohm S (2004) NQO1 activity in the main and the accessory olfactory systems correlates with the zonal topography of projection maps.Eur J Neurosci 19(9):2511–2518CrossRefGoogle Scholar
  19. Hanson MG, Landmesser LT (2004)Normal patterns of spontaneous activity are required for correct motor axon guidance and the expression of specific guidance molecules.Neuron 43(5):687–701PubMedCrossRefGoogle Scholar
  20. Hensch TK (2005) Critical period plasticity in local cortical circuits.Nat Rev Neurosci 6(11):877–888CrossRefGoogle Scholar
  21. Hippenmeyer S, Kramer I, Arber S (2004)Control of neuronal phenotype: what targets tell the cell bodies.Trends Neurosci 27(8):482–488PubMedCrossRefGoogle Scholar
  22. Hirota J, Mombaerts P (2004)The LIM-homeodomain protein Lhx2 is required for complete development of mouse olfactory sensory neurons.Proc Natl Acad Sci USA 101(23):8751–8755PubMedCrossRefGoogle Scholar
  23. Hirota J, Omura M, Mombaerts P (2007) Differential impact of Lhx2 deficiency on expression of class I and class II odorant receptor genes in mouse.Mol Cell Neurosci 34(4):679–688CrossRefGoogle Scholar
  24. Imai T, Sakano H (2007)Roles of odorant receptors in projecting axons in the mouse olfactory system.Curr Opin Neurobiol17:507–515CrossRefGoogle Scholar
  25. Imai T, Suzuki M, Sakano H (2006)Odorant receptor-derived cAMP signals direct axonal targeting.Science 314(5799):657–661PubMedCrossRefGoogle Scholar
  26. Ishii T, Serizawa S, Kohda A, Nakatani H, Shiroishi T, Okumura K, Iwakura Y, Nagawa F, Tsuboi A, Sakano H (2001)Monoallelic expression of the odourant receptor gene and axonal projection of olfactory sensory neurones.Genes Cells 6(1):71–78. Erratum (2001) Genes Cells 6(6):573PubMedCrossRefGoogle Scholar
  27. Iwema CL, Fang H, Kurtz DB, Youngentob SL, Schwob JE (2004)Odorant receptor expression patterns are restored in lesion-recovered rat olfactory epithelium.J Neurosci 24(2):356–369CrossRefGoogle Scholar
  28. Jacobs GH, Williams GA, Cahill H, Nathans J (2007)Emergence of novel color vision in mice engineered to express a human cone photopigment.Science 315(5819):1723–1725PubMedCrossRefGoogle Scholar
  29. Kobayakawa K, Kobayakawa R, Matsumoto H, Oka Y, Imai T, Ikawa M, Okabe M, Ikeda T, Itohara S, Kikusui T, Mori K, Sakano H (2007)Innate versus learned odour processing in the mouse olfactory bulb.Nature 450(7169):503–508PubMedCrossRefGoogle Scholar
  30. Kolterud A, Alenius M, Carlsson L, Bohm S (2004)The Lim homeobox gene Lhx2 is required for olfactory sensory neuron identity.Development 131(21):5319–5326PubMedCrossRefGoogle Scholar
  31. Komiyama T, Luo L (2006)Development of wiring specificity in the olfactory system.Curr Opin Neurobiol 16(1):67–73PubMedCrossRefGoogle Scholar
  32. Komiyama T, Sweeney LB, Schuldiner O, Garcia KC, Luo L (2007)Graded expression of semaphorin-1a cell-autonomously directs dendritic targeting of olfactory projection neurons.Cell 128(2):399–410PubMedCrossRefGoogle Scholar
  33. Kratz E, Dugas JC, Ngai J (2002)Odorant receptor gene regulation: implications from genomic organization.Trends Genet 18(1):29–34PubMedCrossRefGoogle Scholar
  34. Lewcock JW, Reed RR (2004)A feedback mechanism regulates monoallelic odorant receptor expression.Proc Natl Acad Sci USA 101(4):1069–1074PubMedCrossRefGoogle Scholar
  35. Li J, Ishii T, Feinstein P, Mombaerts P (2004) Odorant receptor gene choice is reset by nuclear transfer from mouse olfactory sensory neurons. Nature 428(6981):393–399PubMedCrossRefGoogle Scholar
  36. Lin DM, Wang F, Lowe G, Gold GH, Axel R, Ngai J, Brunet L (2000)Formation of precise connections in the olfactory bulb occurs in the absence of odorant-evoked neuronal activity.Neuron 26(1):69–80PubMedCrossRefGoogle Scholar
  37. Lodovichi C, Belluscio L, Katz LC (2003) Functional topography of connections linking mirrorsymmetric maps in the mouse olfactory bulb. Neuron 38(2):265–276PubMedCrossRefGoogle Scholar
  38. Lomvardas S, Barnea G, Pisapia DJ, Mendelsohn M, Kirkland J, Axel R (2006) Interchromosomal interactions and olfactory receptor choice.Cell 126(2):403–413PubMedCrossRefGoogle Scholar
  39. Luo L, Flanagan JG (2007)Development of continuous and discrete neural maps.Neuron 56(2):284–300PubMedCrossRefGoogle Scholar
  40. Malnic B, Hirono J, Sato T, Buck LB (1999)Combinatorial receptor codes for odors.Cell 96(5):713–723PubMedCrossRefGoogle Scholar
  41. Marks CA, Cheng K, Cummings DM, Belluscio L (2006) Activity-dependent plasticity in the olfactory intrabulbar map.J Neurosci 26(44):11257–11266PubMedCrossRefGoogle Scholar
  42. Miyamichi K, Serizawa S, Kimura HM, Sakano H (2005) Continuous and overlapping expression domains of odorant receptor genes in the olfactory epithelium determine the dorsal/ventral positioning of glomeruli in the olfactory bulb J Neurosci 25(14):3586–3592CrossRefGoogle Scholar
  43. Mombaerts P (2006) Axonal wiring in the mouse olfactory system.Annu Rev Cell Dev Biol22:713–737CrossRefGoogle Scholar
  44. Mombaerts P, Wang F, Dulac C, Chao SK, Nemes A, Mendelsohn M, Edmondson J, Axel R (1996)Visualizing an olfactory sensory map.Cell 87(4):675–686PubMedCrossRefGoogle Scholar
  45. Mori K, Takahashi YK, Igarashi KM, Yamaguchi M (2006)Maps of odorant molecular features in the Mammalian olfactory bulb.Physiol Rev 86(2):409–433PubMedCrossRefGoogle Scholar
  46. Nagawa F, Yoshihara S, Tsuboi A, Serizawa S, Itoh K, Sakano H (2002) Genomic analysis of the murine odorant receptor MOR28 cluster: a possible role of gene conversion in maintaining the olfactory map. Gene 292(1–2):73–80PubMedCrossRefGoogle Scholar
  47. Nakatani H, Serizawa S, Nakajima M, Imai T, Sakano H (2003)Developmental elimination of ectopic projection sites for the transgenic OR gene that has lost zone specificity in the olfactory epithelium.Eur J Neurosci 18(9):2425–2432PubMedCrossRefGoogle Scholar
  48. Ngai J, Chess A, Dowling MM, Necles N, Macagno ER, Axel R (1993) Coding of olfactory information: topography of odorant receptor expression in the catfish olfactory epithelium.Cell 72(5):667–680PubMedCrossRefGoogle Scholar
  49. Nguyen MQ, Zhou Z, Marks CA, Ryba NJ, Belluscio L (2007)Prominent roles for odorant receptor coding sequences in allelic exclusion.Cell 131(5):1009–1017PubMedCrossRefGoogle Scholar
  50. Nishizumi H, Kumasaka K, Inoue N, Nakashima A, Sakano H (2007) Deletion of the core-H region in mice abolishes the expression of three proximal odorant receptor genes in cis.Proc Natl Acad Sci USA 104(50):20067–20072PubMedCrossRefGoogle Scholar
  51. Norlin EM, Alenius M, Gussing F, Fagglund M, Vedin V, Bohm S (2001) Evidence for gradients of gene expression correlating with zonal topography of the olfactory sensory map.Mol Cell Neurosci 18(3):283-295PubMedCrossRefGoogle Scholar
  52. Oka Y, Kobayakawa K, Nishizumi H, Miyamichi K, Hirose S, Tsuboi A, Sakano H.O-MACS, a novel member of the medium-chain acyl-CoA synthetase family, specifically expressed in the olfactory epithelium in a zone-specific manner(2003) Eur J Biochem 270(9):1995–2004PubMedCrossRefGoogle Scholar
  53. Potter SM, Zheng C, Koos DS, Feinstein P, Fraser SE, Mombaerts P (2001) Structure and emergence of specific olfactory glomeruli in the mouse.J Neurosci 21(24):9713–9723PubMedGoogle Scholar
  54. Ray A, van Naters WG, Shiraiwa T, Carlson JR (2007) Mechanisms of odor receptor gene choice in Drosophila. Neuron 53(3):353–369PubMedCrossRefGoogle Scholar
  55. Ressler KJ, Sullivan SL, Buck LB1993)A zonal organization of odorant receptor gene expression in the olfactory epithelium.Cell 73(3):597–609PubMedCrossRefGoogle Scholar
  56. Ressler KJ, Sullivan SL, Buck LB1994)Information coding in the olfactory system: evidence for a stereotyped and highly organized epitope map in the olfactory bulb.Cell 79(7):12451255PubMedCrossRefGoogle Scholar
  57. Rothman A, Feinstein P, Hirota J, Mombaerts P2005)The promoter of the mouse odorant receptor gene M71.Mol Cell Neurosci 28(3):535–546PubMedCrossRefGoogle Scholar
  58. Saucier D, Astic L (1986) Analysis of the topographical organization of olfactory epithelium projections in the rat. Brain Res Bull 16(4):455–462PubMedCrossRefGoogle Scholar
  59. Schwarting GA, Kostek C, Ahmad N, Dibble C, Pays L, Püschel AW (2000)Semaphorin 3A is required for guidance of olfactory axons in mice.J Neurosci 20(20):7691–7697PubMedGoogle Scholar
  60. Sengoku S, Ishii T, Serizawa S, Nakatani H, Nagawa F, Tsuboi A, Sakano H (2001) Axonal projection of olfactory sensory neurons during the developmental and regeneration processes. Neuroreport 12(5):1061–1066PubMedCrossRefGoogle Scholar
  61. Serizawa S, Ishii T, Nakatani H, Tsuboi A, Nagawa F, Asano M, Sudo K, Sakagami J, Sakano H, Ijiri T, Matsuda Y, Suzuki M, Yamamori T, Iwakura Y, Sakano H (2000) Mutually exclusive expression of odorant receptor transgenes. Nat Neurosci 3(7):687–693PubMedCrossRefGoogle Scholar
  62. Serizawa S, Miyamichi K, Nakatani H, Suzuki M, Saito M, Yoshihara Y, Sakano H (2003) Negative feedback regulation ensures the one receptor-one olfactory neuron rule in mouse. Science 302(5653):2088–2094PubMedCrossRefGoogle Scholar
  63. Serizawa S, Miyamichi K, Sakano H (2004) One neuron-one receptor rule in the mouse olfactory system. Trends Genet 20(12):648–653PubMedCrossRefGoogle Scholar
  64. Serizawa S, Miyamichi K, Takeuchi H, Yamagishi Y, Suzuki M, Sakano H (2006) A neuronal identity code for the odorant receptor-specific and activity-dependent axon sorting. Cell 127(5):1057–1069PubMedCrossRefGoogle Scholar
  65. Shen K, Bargmann CI (2003) The immunoglobulin superfamily protein SYG-1 determines the location of specific synapses in C. elegans. Cell 112(5):619–630PubMedCrossRefGoogle Scholar
  66. Song HJ, Poo MM (1999) Signal transduction underlying growth cone guidance by diffusible factors. Curr Opin Neurobiol 9(3):355–363PubMedCrossRefGoogle Scholar
  67. St John JA, Pasquale EB, Key B (2002) EphA receptors and ephrin-A ligands exhibit highly regulated spatial and temporal expression patterns in the developing olfactory system. Brain Res Dev Brain Res 138(1):1–14PubMedCrossRefGoogle Scholar
  68. Strotmann J, Wanner I, Krieger J, Raming K, Breer H (1992) Expression of odorant receptors in spatially restricted subsets of chemosensory neurones. Neuroreport 3(12):1053–1056PubMedCrossRefGoogle Scholar
  69. Strotmann J, Conzelmann S, Beck A, Feinstein P, Breer H, Mombaerts P (2000) Local permutations in the glomerular array of the mouse olfactory bulb. J Neurosci 20(18):6927–6938PubMedGoogle Scholar
  70. Strotmann J, Levai O, Fleischer J, Schwarzenbacher K, Breer H (2004) Olfactory receptor proteins in axonal processes of chemosensory neurons. J Neurosci 24(35):7754–7761PubMedCrossRefGoogle Scholar
  71. Taniguchi M, Nagao H, Takahashi YK, Yamaguchi M, Mitsui S, Yagi T, Mori K, Shimizu T (2003) Distorted odor maps in the olfactory bulb of semaphorin 3A-deficient mice. J Neurosci 23(4):1390–1397PubMedGoogle Scholar
  72. Trinh K, Storm DR (2003) Vomeronasal organ detects odorants in absence of signaling through main olfactory epithelium. Nat Neurosci 6(5):519–525PubMedGoogle Scholar
  73. Tsuboi A, Miyazaki T, Imai T, Sakano H (2006) Olfactory sensory neurons expressing class I odorant receptors converge their axons on an antero-dorsal domain of the olfactory bulb in the mouse. Eur J Neurosci 23(6):1436–1444PubMedCrossRefGoogle Scholar
  74. Vassalli A, Rothman A, Feinstein P, Zapotocky M, Mombaerts P (2002) Minigenes impart odorant receptor-specific axon guidance in the olfactory bulb. Neuron 35(4):681–696PubMedCrossRefGoogle Scholar
  75. Vassar R, Ngai J, Axel R (1993) Spatial segregation of odorant receptor expression in the mammalian olfactory epithelium. Cell 74(2):309–318PubMedCrossRefGoogle Scholar
  76. Vassar R, Chao SK, Sitcheran R, Nuñez JM, Vosshall LB, Axel R (1994) Topographic organization of sensory projections to the olfactory bulb. Cell 79(6):981–991PubMedCrossRefGoogle Scholar
  77. Vrieseling E, Arber S (2006) Target-induced transcriptional control of dendritic patterning and connectivity in motor neurons by the ETS gene Pea3. Cell 127(7):1439–1452PubMedCrossRefGoogle Scholar
  78. Walz A, Rodriguez I, Mombaerts P (2002) Aberrant sensory innervation of the olfactory bulb in neuropilin-2 mutant mice. J Neurosci 22(10):4025–4035PubMedGoogle Scholar
  79. Wang F, Nemes A, Mendelsohn M, Axel R (1998) Odorant receptors govern the formation of a precise topographic map. Cell 93(1):47–60PubMedCrossRefGoogle Scholar
  80. Wang SS, Lewcock JW, Feinstein P, Mombaerts P, Reed RR (2004) Genetic disruptions of O/E2 and O/E3 genes reveal involvement in olfactory receptor neuron projection. Development 131(6):1377–1388PubMedCrossRefGoogle Scholar
  81. West AE, Griffith EC, Greenberg ME (2002) Regulation of transcription factors by neuronal activity. Nat Rev Neurosci 3(12):921–931PubMedCrossRefGoogle Scholar
  82. Yan Z, Tan J, Qin C, Lu Y, Ding C, Luo M (2008) Precise circuitry links bilaterally symmetric olfactory maps. Neuron 58(4):613–624PubMedCrossRefGoogle Scholar
  83. Yoshihara Y, Kawasaki M, Tamada A, Fujita H, Hayashi H, Kagamiyama H, Mori K (1997) OCAM: A new member of the neural cell adhesion molecule family related to zone-to-zone projection of olfactory and vomeronasal axons. J Neurosci 17(15):5830–5842PubMedGoogle Scholar
  84. Yu CR, Power J, Barnea G, O'Donnell S, Brown HE, Osborne J, Axel R, Gogos JA (2004) Spontaneous neural activity is required for the establishment and maintenance of the olfactory sensory map. Neuron 42(4):553–566PubMedCrossRefGoogle Scholar
  85. Zhang X, Firestein S (2002) The olfactory receptor gene superfamily of the mouse. Nat Neurosci 5(2):124–133PubMedGoogle Scholar
  86. Zhang X, Rogers M, Tian H, Zhang X, Zou DJ, Liu J, Ma M, Shepherd GM, Firestein SJ (2004) High-throughput microarray detection of olfactory receptor gene expression in the mouse. Proc Natl Acad Sci USA 101(39):14168–14173PubMedCrossRefGoogle Scholar
  87. Zhang X, Zhang X, Firestein S (2007) Comparative genomics of odorant and pheromone receptor genes in rodents. Genomics 89(4):441–450PubMedCrossRefGoogle Scholar
  88. Zhao H, Reed RR (2001) X inactivation of the OCNC1 channel gene reveals a role for activity-dependent competition in the olfactory system. Cell 104(5):651–660PubMedCrossRefGoogle Scholar
  89. Zhao H, Ivic L, Otaki JM, Hashimoto M, Mikoshiba K, Firestein S (1998) Functional expression of a mammalian odorant receptor. Science 279(5348):237–242PubMedCrossRefGoogle Scholar
  90. Zheng C, Feinstein P, Bozza T, Rodriguez I, Mombaerts P (2000) Peripheral olfactory projections are differentially affected in mice deficient in a cyclic nucleotide-gated channel subunit. Neuron 26(1):81–91PubMedCrossRefGoogle Scholar
  91. Zou Z, Buck LB (2006) Combinatorial effects of odorant mixes in olfactory cortex. Science 311(5766):1477–1481PubMedCrossRefGoogle Scholar
  92. Zou DJ, Feinstein P, Rivers AL, Mathews GA, Kim A, Greer CA, Mombaerts P, Firestein S (2004) Postnatal refinement of peripheral olfactory projections. Science 304(5679):1976–1979PubMedCrossRefGoogle Scholar
  93. Zou DJ, Chesler AT, Le Pichon CE, Kuznetsov A, Pei X, Hwang EL, Firestein S (2007) Absence of adenylyl cyclase 3 perturbs peripheral olfactory projections in mice. J Neurosci 27(25):6675–6683PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2008

Authors and Affiliations

  • T. Imai
    • 1
  • H. Sakano
    • 1
  1. 1.Department of Biophysics and Biochemistry, Graduate School of ScienceThe University of TokyoTokyoJapan

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