Skip to main content
SpringerLink
Log in

Stem Cells of the Adult Olfactory Epithelium

  • Chapter
Neural Development and Stem Cells

Part of the book series: Contemporary Neuroscience ((CNEURO))

Abstract

The peripheral olfactory system consists of the olfactory (neuro)epithelium lining the posterodorsal nasal cavity, and the olfactory nerve connecting the sensory neurons in the periphery with their central nervous system (CNS) target, the olfactory bulb (1,2). The epithelium is composed of a handful of easily distinguishable cell types, including basal cells, olfactory sensory neurons (OSNs), nonneuronal supporting or sustentacular (Sus) cells, and Bowman duct/gland assemblies (3). The peripheral olfactory system is readily accessible and can be safely biopsied with minimal discomfort or risk, thereby offering a unique glimpse of a part of the nervous system (4–6). In addition, the capacity of the peripheral olfactory system to accomplish anatomical reconstitution and functional restoration from injury has suggested that the epithelium retains a population of neurocompetent stem cells (i.e., capable of producing neurons) which, given their accessibility, may be a valuable addition to our therapeutic and analytical armamentarium. Moreover, the ensheathing cells of the olfactory nerve have been effective in promoting behavioral and neuroanatomical recovery after spinal cord injury in experimental animals (7).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 149.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Graziadei, P. P. C. (1990) Olfactory development. In Development of Sensory Systems in Mammals (Coleman, J. R., ed.,) John Wiley, New York.

    Google Scholar 

  2. Graziadei, P. P. C. (1974) The olfactory organ of vertebrates: a survey. In Essays on Structure and Function in the Nervous System (Bellairs, R. and Gray, E. G., eds.,) Clarendon, London, pp. 191–222.

    Google Scholar 

  3. Schwob, J. E. (2002) Neural regeneration and the peripheral olfactory system. Anat. Rec. 269, 33–49.

    Article  PubMed  Google Scholar 

  4. Rawson, N. E., Gomez, G., Cowart, B., and Restrepo, D. (1998) The use of olfactory receptor neurons (ORNs) from biopsies to study changes in aging and neurodegenerative diseases. Ann. NY Acad. Sci. 855, 701–707.

    Article  PubMed  CAS  Google Scholar 

  5. Lane, A. P., Gomez, G., Dankulich, T., Wang, H., Bolger, W. E., and Rawson, N. E. (2002) The superior turbinate as a source of functional human olfactory receptor neurons. Laryngoscope 112, 1183–1189.

    Article  PubMed  Google Scholar 

  6. Rawson, N. E. and Gomez, G. (2002) Cell and molecular biology of human olfaction. Microsc. Res. Tech. 58, 142–151.

    Article  PubMed  CAS  Google Scholar 

  7. Raisman, G. (2001) Olfactory ensheathing cells—another miracle cure for spinal cord injury? Nat. Rev. Neurosci. 2, 369–375.

    Article  PubMed  CAS  Google Scholar 

  8. Cuschieri, A. and Bannister, L. H. (1975) The development of the olfactory mucosa in the mouse: light microscopy. J. Anat. 119, 277–286.

    PubMed  CAS  Google Scholar 

  9. Cuschieri, A. and Bannister, L. H. (1975) The development of the olfactory mucosa in the mouse: electron microscopy. J. Anat. 119, 471–498.

    PubMed  CAS  Google Scholar 

  10. Couly, G. F. and Le Douarin, N. M. (1985) Mapping of the early neural primordium in quail-chick chimeras. I. Developmental relationships between placodes, facial ectoderm, and prosencephalon. Dev. Biol. 110, 422–439.

    Article  PubMed  CAS  Google Scholar 

  11. Farbman, A. I. and Squinto, L. M. (1985) Early development of olfactory receptor cell axons. J. Neurochem. 44, 1459–1464.

    Article  PubMed  Google Scholar 

  12. Schwanzel-Fukuda, M. and Pfaff, D. W. (1990) The migration of luteinizing hormone-releasing hormone (LHRH) neurons from the medial olfactory placode into the medial basal forebrain. Experientia 46, 956–962.

    Article  PubMed  CAS  Google Scholar 

  13. Schwanzel-Fukuda, M. (1999) Origin and migration of luteinizing hormone-releasing hormone neurons in mammals. Microsc. Res. Tech. 44, 2–10.

    Article  PubMed  CAS  Google Scholar 

  14. Nagahara, Y. (1940) Experimentelle Studien uber die histologiischen Veranderungen des Geruchsorgan nach der Olfactoriusdurschneidung. Beitrage zur Kenntnis des feineren Baus des Geruchsorgans. Jpn. J. Med. Sci. V. Pathol. 5, 165–169.

    Google Scholar 

  15. Bodian, D. A. and Howe, H. A. (1941) Experimental studies on intraneural spread of poliomyelitis virus. Bull. Johns Hopkins Hosp. 68, 248–267.

    Google Scholar 

  16. Moulton, D. G., Celebi, G., and Fink, R. P. (1970) Olfaction in mammals—two aspects: proliferation of cells in the olfactory epithelium and sensitivity to odours. In Ciba Foundation Symposium on Taste and Smell in Vertebrates (Wolstenholme, G. E. W. and Knight, J., eds.,) Churchill, London, pp. 227–250.

    Google Scholar 

  17. Graziadei, P. P. C. and Metcalf, J. F. (1971) Autoradiographic and ultrastructural observations on the frog’s olfactory mucosa. Z. Zellforsch. Mikrosk. Anat. 116, 305–318.

    Article  PubMed  CAS  Google Scholar 

  18. Moulton, D. G. (1975) Cell renewal in the olfactory epithelium. In Olfaction and Taste, V (Denton, D. A. and Coghlan, J. P., eds.,) Academic Press, New York, pp. 111–114.

    Google Scholar 

  19. Graziadei, P. P. C. (1973) Cell dynamics in the olfactory mucosa. Tissue Cell 5, 113–131.

    PubMed  CAS  Google Scholar 

  20. Graziadei, P. P. C. and Monti Graziadei, G. A. (1978) Continuous nerve cell renewal in the olfactory system. In Handbook of Sensory Physiology, Vol. IX (Jacobson, M., ed.,) Springer-Verlag, Berlin, pp. 55–82.

    Google Scholar 

  21. Graziadei, P. P. C. and Monti Graziadei, G. A. (1979) Neurogenesis and neuron regeneration in the olfactory system of mammals. I. Morphological aspects of differentiation and structural organization of the olfactory sensory neurons. J. Neurocytol. 8, 1–18.

    Article  PubMed  CAS  Google Scholar 

  22. Verhaagen, J., Oestreicher, A. B., Gispen, W. H., and Margolis, F. L. (1989) The expression of the growth associated protein B50/GAP43 in the olfactory system of neonatal and adult rats. J. Neurosci. 9, 683–691.

    PubMed  CAS  Google Scholar 

  23. Meiri, K. F., Bickerstaff, L. E., and Schwob, J. E. (1991) Monoclonal antibodies show that kinase C phosphorylation of GAP-43 during axonogenesis is both spatially and temporally restricted in vivo. J. Cell Biol. 112, 991–1005.

    Article  PubMed  CAS  Google Scholar 

  24. Schwob, J. E., Szumowski, K. E., and Stasky, A. A. (1992) Olfactory sensory neurons are trophically dependent on the olfactory bulb for their prolonged survival. J. Neurosci. 12, 3896–3919.

    PubMed  CAS  Google Scholar 

  25. Mackay-Sim, A. and Kittel, P. W. (1991) On the life span of olfactory receptor neurons. Eur. J. Neurosci. 3, 209–215.

    Article  PubMed  Google Scholar 

  26. Harding, J., Graziadei, P. P. C., Monti Graziadei, G. A., and Margolis, F. L. (1977) Denervation in the primary olfactory pathway of mice. IV. Biochemical and morphological evidence for neuronal replacement following nerve section. Brain Res. 132, 11–28.

    Article  PubMed  CAS  Google Scholar 

  27. Monti Graziadei, G. A. and Graziadei, P. P. C. (1979) Neurogenesis and neuron regeneration in the olfactory system of mammals. II. Degeneration and reconstitution of the olfactory sensory neurons after axotomy. J. Neurocytol. 8, 197–213.

    Article  Google Scholar 

  28. Costanzo, R. M. and Graziadei, P. P. C. (1983) A quantitative analysis of changes in the olfactory epithelium following bulbectomy in hamster. J. Comp. Neurol. 215, 370–381.

    Article  PubMed  CAS  Google Scholar 

  29. Costanzo, R. M. (1984) Comparison of neurogenesis and cell replacement in the hamster olfactory system with and without a target (olfactory bulb). Brain Res. 307, 295–301.

    Article  PubMed  CAS  Google Scholar 

  30. Costanzo, R. M. (1985) Neural regeneration and functional reconnection following olfactory nerve transection in hamster. Brain Res. 361, 258–266.

    Article  PubMed  CAS  Google Scholar 

  31. Costanzo, R. M. (2000) Rewiring the olfactory bulb: changes in odor maps following recovery from nerve transection. Chem. Senses 25, 199–205.

    Article  PubMed  CAS  Google Scholar 

  32. Schwob, J. E., Youngentob, S. L., and Mezza, R. C. (1995) Reconstitution of the rat olfactory epithelium after methyl bromide-induced lesion. J. Comp. Neurol. 359, 15–37.

    Article  PubMed  CAS  Google Scholar 

  33. Holbrook, E. H., Szumowski, K. E. and Schwob, J. E. (1995) An immunochemical, ultra-structural, and developmental characterization of the horizontal basal cells of rat olfactory epithelium. J. Comp. Neurol. 363, 129–146.

    Article  PubMed  CAS  Google Scholar 

  34. Schwartz Levey, M., Chikaraishi, D. M., and Kauer, J. S. (1991) Characterization of potential precursor populations in the mouse olfactory epithelium using immunocytochemistry and autoradiography. J. Neurosci. 11, 3556–3664.

    PubMed  CAS  Google Scholar 

  35. Huard, J. M. and Schwob, J. E. (1995) Cell cycle of globose basal cells in rat olfactory epithelium. Dev. Dyn. 203, 17–26.

    PubMed  CAS  Google Scholar 

  36. Schwartz Levey, M., Cinelli, A. R., and Kauer, J. S. (1992) Intracellular injection of vital dyes into single cells in the salamander olfactory epithelium. Neurosci. Lett. 140, 265–269.

    Article  PubMed  CAS  Google Scholar 

  37. Caggiano, M., Kauer, J. S., and Hunter, D. D. (1994) Globose basal cells are neuronal progenitors in the olfactory epithelium: a lineage analysis using a replication-incompetent retrovirus. Neuron 13, 339–352.

    Article  PubMed  CAS  Google Scholar 

  38. Schwob, J. E., Huard, J. M., Luskin, M. B., and Youngentob, S. L. (1994) Retroviral lineage studies of the rat olfactory epithelium. Chem. Senses 19, 671–682.

    Article  PubMed  CAS  Google Scholar 

  39. Guillemot, F., Lo, L. C., Johnson, J. E., Auerbach, A., Anderson, D. J., and Joyner, A. L. (1993) Mammalian achaete-scute homolog 1 is required for the early development of olfactory and autonomic neurons. Cell 75, 463–476.

    Article  PubMed  CAS  Google Scholar 

  40. Gordon, M. K., Mumm, J. S., Davis, R. A., Holcomb, J. D., and Calof, A. L. (1995) Dynamics of MASH1 expression in vitro and in vivo suggest a non-stem cell site of MASH1 action in the olfactory receptor neuron lineage. Mol. Cell. Neurosci. 6, 363–379.

    Article  PubMed  CAS  Google Scholar 

  41. Cau, E., Gradwohl, G., Fode, C., and Guillemot, F. (1997) Mash1 activates a cascade of bHLH regulators in olfactory neuron progenitors. Development 124, 1611–1621.

    PubMed  CAS  Google Scholar 

  42. Mumm, J. S., Shou, J., and Calof, A. L. (1996) Colony-forming progenitors from mouse olfactory epithelium: evidence for feedback regulation of neuron production. Proc. Natl. Acad. Sci. USA 93, 11167–11172.

    Article  PubMed  CAS  Google Scholar 

  43. Calof, A. L., Mumm, J. S., Rim, P. C., and Shou, J. (1998) The neuronal stem cell of the olfactory epithelium. J. Neurobiol. 36, 190–205.

    Article  PubMed  CAS  Google Scholar 

  44. Cau, E., Casarosa, S., and Guillemot, F. (2002) Mash1 and Ngn1 control distinct steps of determination and differentiation in the olfactory sensory neuron lineage. Development 129, 1871–1880.

    PubMed  CAS  Google Scholar 

  45. Wu, H. H., Ivkovic, S., Murray, R. C., et al. (2003) Autoregulation of neurogenesis by GDF11. Neuron 37, 197–207.

    Article  PubMed  CAS  Google Scholar 

  46. Iwema, C. L., Fang, H., Kurtz, D. B., Youngentob, S. L., and Schwob, J. E. (2004) Odorant receptor expression patterns are restored in lesion-recovered rat olfactory epithelium. J. Neurosci. 24, 356–369.

    Article  PubMed  CAS  Google Scholar 

  47. Cotsarelis, G., Cheng, S. Z., Dong, G., Sun, T. T., and Lavker, R. M. (1989) Existence of slow-cycling limbal epithelial basal cells that can be preferentially stimulated to proliferate: implications on epithelial stem cells. Cell 57, 201–209.

    Article  PubMed  CAS  Google Scholar 

  48. Potten, C. S. and Loeffler, M. (1990) Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. Development 110, 1001–1020.

    Google Scholar 

  49. Morris, R. J. and Potten, C. S. (1994) Slowly cycling (label-retaining) epidermal cells behave like clonogenic stem cells in vitro. Cell Prolif. 27, 279–289.

    PubMed  CAS  Google Scholar 

  50. Potten, C. S. (1998) Stem cells in gastrointestinal epithelium: numbers, characteristics and death. Philos. Trans. R. Soc. Lond. B Biol. Sci. 353, 821–830.

    Article  PubMed  CAS  Google Scholar 

  51. Watt, F. M. and Hogan, B. L. (2000) Out of Eden: stem cells and their niches. Science 287, 1427–1430.

    Article  PubMed  CAS  Google Scholar 

  52. Lavker, R. M. and Sun, T. T. (2003) Epithelial stem cells: the eye provides a vision. Eye 17, 937–942.

    Article  PubMed  CAS  Google Scholar 

  53. Goldstein, B. J. and Schwob, J. E. (1996) Analysis of the globose basal cell compartment in rat olfactory epithelium using GBC-1, a new monoclonal antibody against globose basal cells. J. Neurosci. 16, 4005–4016.

    PubMed  CAS  Google Scholar 

  54. Huard, J. M., Youngentob, S. L., Goldstein, B. J., Luskin, M. B., and Schwob, J. E. (1998) Adult olfactory epithelium contains multipotent progenitors that give rise to neurons and non-neural cells. J. Comp. Neurol. 400, 469–486.

    Article  PubMed  CAS  Google Scholar 

  55. Murray, R. C., Navi, D., Fesenko, J., Lander, A. D., and Calof, A. L. (2003) Widespread defects in the primary olfactory pathway caused by loss of Mash1 function. J. Neurosci. 23, 1769–1780.

    PubMed  CAS  Google Scholar 

  56. Chen, X., Fang, H., and Schwob, J. E. (2004) Multipotency of purified, transplanted globose basal cells in olfactory epithelium. J. Comp. Neurol. 469, 457–474.

    Article  PubMed  Google Scholar 

  57. Goldstein, B. J., Fang, H., Youngentob, S. L., and Schwob, J. E. (1998) Transplantation of multipotent progenitors from the adult olfactory epithelium. NeuroReport 9, 1611–1617.

    Article  PubMed  CAS  Google Scholar 

  58. Satoh, M. and Yoshida, T. (2000) Expression of neural properties in olfactory cytokeratin-positive basal cell line. Brain Res. Dev. Brain Res. 121, 219–222.

    Article  PubMed  CAS  Google Scholar 

  59. Satoh, M. and Takeuchi, M. (1995) Induction of NCAM expression in mouse olfactory keratin-positive basal cells in vitro. Brain Res. Dev. Brain Res. 87, 111–119.

    Article  PubMed  CAS  Google Scholar 

  60. Chen, X. C. (2003) Functional Capacity of Progenitor Cells in the Olfactory Epithelium. Ph. D. thesis in Cell, Molecular, and Developmental Biology, Tufts University, Boston, MA.

    Google Scholar 

  61. Manglapus, G. L. (2003) Molecular Mechanisms for Progenitor Cell Regulation in the Mammalian Peripheral Olfactory System. Ph. D. thesis in Neuroscience and Physiology, SUNY-Syracuse.

    Google Scholar 

  62. Davis, R. L. and Turner, D. L. (2001) Vertebrate hairy and Enhancer of split related proteins: transcriptional repressors regulating cellular differentiation and embryonic patterning. Oncogene 20, 8342–8357.

    Article  PubMed  CAS  Google Scholar 

  63. Fisher, A. and Caudy, M. (1998) The function of hairy-related bHLH repressor proteins in cell fate decisions. BioEssays 20, 298–306.

    Article  PubMed  CAS  Google Scholar 

  64. Cau, E., Gradwohl, G., Casarosa, S., Kageyama, R., and Guillemot, F. (2000) Hes genes regulate sequential stages of neurogenesis in the olfactory epithelium. Development 127, 2323–2332.

    PubMed  CAS  Google Scholar 

  65. Suzuki, Y., Mizoguchi, I., Nishiyama, H., Takeda, M., and Obara, N. (2003) Expression of Hes6 and NeuroD in the olfactory epithelium, vomeronasal organ and nonsensory patches. Chem Senses 28, 197–205.

    Article  PubMed  CAS  Google Scholar 

  66. Iso, T., Kedes, L., and Hamamori, Y. (2003) HES and HERP families: multiple effectors of the Notch signaling pathway. J. Cell. Physiol. 194, 237–255.

    Article  PubMed  CAS  Google Scholar 

  67. Carr, V. M. and Farbman, A. I. (1992) Ablation of the olfactory bulb up-regulates the rate of neurogenesis and induces precocious cell death in olfactory epithelium. Exp. Neurol. 115, 55–59.

    Article  PubMed  CAS  Google Scholar 

  68. Farbman, A. I., Brunjes, P. C., Rentfro, L., Michas, J., and Ritz, S. (1988) The effect of unilateral naris occlusion on cell dynamics in the developing rat olfactory epithelium. J. Neuro-biol. 19, 681–693.

    Google Scholar 

  69. Farbman, A. I. (1990) Olfactory neurogenesis: genetic or environmental controls? Trends Neurosci. 13, 362–365.

    Article  PubMed  CAS  Google Scholar 

  70. Calof, A. L. and Chikaraishi, D. M. (1989) Analysis of neurogenesis in a mammalian neuroepithelium: proliferation and differentiation of an olfactory neuron precursor in vitro. Neuron 3, 115–127.

    Article  PubMed  CAS  Google Scholar 

  71. DeHamer, M. K., Guevara, J. L., Hannon, K., Olwin, B. B., and Calof, A. L. (1994) Genesis of olfactory receptor neurons in vitro: regulation of progenitor cell divisions by fibro-blast growth factors. Neuron 13, 1083–1097.

    Article  PubMed  CAS  Google Scholar 

  72. Calof, A. L. (1995) Intrinsic and extrinsic factors regulating vertebrate neurogenesis. Curr. Opin. Neurobiol. 5, 19–27.

    Article  PubMed  CAS  Google Scholar 

  73. Newman, M. P., Feron, F., and Mackay-Sim, A. (2000) Growth factor regulation of neurogenesis in adult olfactory epithelium. Neuroscience 99, 343–350.

    Article  PubMed  CAS  Google Scholar 

  74. Hsu, P., Yu, F., Feron, F., Pickles, J. O., Sneesby, K., and Mackay-Sim, A. (2001) Basic fibroblast growth factor and fibroblast growth factor receptors in adult olfactory epithelium. Brain Res. 896, 188–197.

    Article  PubMed  CAS  Google Scholar 

  75. Goldstein, B. J., Wolozin, B. L., and Schwob, J. E. (1997) FGF2 suppresses neuronogenesis of a cell line derived from rat olfactory epithelium. J. Neurobiol. 33, 411–428.

    Article  PubMed  CAS  Google Scholar 

  76. Mahanthappa, N. K. and Schwarting, G. A. (1993) Peptide growth factor control of olfactory neurogenesis and neuron survival in vitro: roles of EGF and TGF-betas. Neuron 10, 293–305.

    Article  PubMed  CAS  Google Scholar 

  77. Farbman, A. I. and Buchholz, J. A. (1996) Transforming growth factor-alpha and other growth factors stimulate cell division in olfactory epithelium in vitro. J. Neurobiol. 30, 267–280.

    Article  PubMed  CAS  Google Scholar 

  78. Ezeh, P. I. and Farbman, A. I. (1998) Differential activation of ErbB receptors in the rat olfactory mucosa by transforming growth factor-alpha and epidermal growth factor in vivo. J. Neurobiol. 37, 199–210.

    Article  PubMed  CAS  Google Scholar 

  79. Getchell, T. V., Narla, R. K., Little, S., Hyde, J. F., and Getchell, M. L. (2000) Horizontal basal cell proliferation in the olfactory epithelium of transforming growth factor-alpha transgenic mice. Cell Tissue Res. 299, 185–192.

    PubMed  CAS  Google Scholar 

  80. Salehi-Ashtiani, K. and Farbman, A. I. (1996) Expression of neu and Neu differentiation factor in the olfactory mucosa of rat. Int. J. Dev. Neurosci. 14, 801–811.

    Article  PubMed  CAS  Google Scholar 

  81. Shou, J., Rim, P. C., and Calof, A. L. (1999) BMPs inhibit neurogenesis by a mechanism involving degradation of a transcription factor. Nat. Neurosci. 2, 339–345.

    Article  PubMed  CAS  Google Scholar 

  82. Shou, J., Murray, R. C., Rim, P. C., and Calof, A. L. (2000) Opposing effects of bone morphogenetic proteins on neuron production and survival in the olfactory receptor neuron lineage. Development 127, 5403–5413.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, MA

    James E. Schwob & Woochan Jang

Authors
  1. James E. Schwob
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Woochan Jang
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. National Institute on Aging, Baltimore, MD

    Mahendra S. Rao MBBS, PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Schwob, J.E., Jang, W. (2006). Stem Cells of the Adult Olfactory Epithelium. In: Rao, M.S. (eds) Neural Development and Stem Cells. Contemporary Neuroscience. Humana Press. https://doi.org/10.1385/1-59259-914-1:219

Download citation

Publish with us

Policies and ethics

Search

Navigation