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Proc Natl Acad Sci U S A. Oct 1, 1996; 93(20): 11167–11172.
PMCID: PMC38302

Colony-forming progenitors from mouse olfactory epithelium: evidence for feedback regulation of neuron production.

Abstract

The mammalian olfactory epithelium (OE) supports continual neurogenesis throughout life, suggesting that a neuronal stem cell exists in this system. In tissue culture, however, the capacity of the OE for neurogenesis ceases after a few days. In an attempt to identify conditions that support the survival of neuronal stem cells, a population of neuronal progenitors was isolated from embryonic mouse OE and cultured in defined serum-free medium. The vast majority of cells rapidly gave rise to neurons, which died shortly thereafter. However, when purified progenitors were co-cultured with cells derived from the stroma underlying the OE, a small subpopulation (0.07-0.1%) gave rise to proliferative colonies. A morphologically identifiable subset of these colonies generated new neurons as late as 7 days in vitro. Interestingly, development of these neuronal colonies was specifically inhibited when purified progenitors were plated onto stromal feeder cells in the presence of a large excess of differentiated OE neurons. These results indicate that a rare cell type, with the potential to undergo prolonged neurogenesis, can be isolated from mammalian OE and that stroma-derived factors are important in supporting neurogenesis by this cell. The data further suggest that differentiated neurons provide a signal that feeds back to inhibit production of new neurons by their own progenitors.

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  • Calof AL. Intrinsic and extrinsic factors regulating vertebrate neurogenesis. Curr Opin Neurobiol. 1995 Feb;5(1):19–27. [PubMed]
  • Graziadei PP. Cell dynamics in the olfactory mucosa. Tissue Cell. 1973;5(1):113–131. [PubMed]
  • Harding J, Graziadei PP, Monti Graziadei GA, Margolis FL. Denervation in the primary olfactory pathway of mice. IV. Biochemical and morphological evidence for neuronal replacement following nerve section. Brain Res. 1977 Aug 19;132(1):11–28. [PubMed]
  • Graziadei GA, Graziadei PP. Neurogenesis and neuron regeneration in the olfactory system of mammals. II. Degeneration and reconstitution of the olfactory sensory neurons after axotomy. J Neurocytol. 1979 Apr;8(2):197–213. [PubMed]
  • Calof AL, Chikaraishi DM. Analysis of neurogenesis in a mammalian neuroepithelium: proliferation and differentiation of an olfactory neuron precursor in vitro. Neuron. 1989 Jul;3(1):115–127. [PubMed]
  • Caggiano M, Kauer JS, Hunter DD. Globose basal cells are neuronal progenitors in the olfactory epithelium: a lineage analysis using a replication-incompetent retrovirus. Neuron. 1994 Aug;13(2):339–352. [PubMed]
  • Schwartz Levey M, Chikaraishi DM, Kauer JS. Characterization of potential precursor populations in the mouse olfactory epithelium using immunocytochemistry and autoradiography. J Neurosci. 1991 Nov;11(11):3556–3564. [PubMed]
  • DeHamer MK, Guevara JL, Hannon K, Olwin BB, Calof AL. Genesis of olfactory receptor neurons in vitro: regulation of progenitor cell divisions by fibroblast growth factors. Neuron. 1994 Nov;13(5):1083–1097. [PubMed]
  • Gordon MK, Mumm JS, Davis RA, Holcomb JD, Calof AL. 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. 1995 Aug;6(4):363–379. [PubMed]
  • Calof AL, Lander AD. Relationship between neuronal migration and cell-substratum adhesion: laminin and merosin promote olfactory neuronal migration but are anti-adhesive. J Cell Biol. 1991 Nov;115(3):779–794. [PMC free article] [PubMed]
  • Holcomb JD, Mumm JS, Calof AL. Apoptosis in the neuronal lineage of the mouse olfactory epithelium: regulation in vivo and in vitro. Dev Biol. 1995 Nov;172(1):307–323. [PubMed]
  • Gennarini G, Rougon G, Deagostini-Bazin H, Hirn M, Goridis C. Studies on the transmembrane disposition of the neural cell adhesion molecule N-CAM. A monoclonal antibody recognizing a cytoplasmic domain and evidence for the presence of phosphoserine residues. Eur J Biochem. 1984 Jul 2;142(1):57–64. [PubMed]
  • Gray GE, Sanes JR. Migratory paths and phenotypic choices of clonally related cells in the avian optic tectum. Neuron. 1991 Feb;6(2):211–225. [PubMed]
  • Friedrich G, Soriano P. Promoter traps in embryonic stem cells: a genetic screen to identify and mutate developmental genes in mice. Genes Dev. 1991 Sep;5(9):1513–1523. [PubMed]
  • Doucette R. Glial progenitor cells of the nerve fiber layer of the olfactory bulb: effect of astrocyte growth media. J Neurosci Res. 1993 Jun 15;35(3):274–287. [PubMed]
  • Graziadei PP, Graziadei GA. 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. 1979 Feb;8(1):1–18. [PubMed]
  • Calof AL, Hagiwara N, Holcomb JD, Mumm JS, Shou J. Neurogenesis and cell death in olfactory epithelium. J Neurobiol. 1996 May;30(1):67–81. [PubMed]
  • Pixley SK. CNS glial cells support in vitro survival, division, and differentiation of dissociated olfactory neuronal progenitor cells. Neuron. 1992 Jun;8(6):1191–1204. [PubMed]
  • Mahanthappa NK, Schwarting GA. Peptide growth factor control of olfactory neurogenesis and neuron survival in vitro: roles of EGF and TGF-beta s. Neuron. 1993 Feb;10(2):293–305. [PubMed]
  • Chuah MI, Au C. Olfactory Schwann cells are derived from precursor cells in the olfactory epithelium. J Neurosci Res. 1991 Jun;29(2):172–180. [PubMed]
  • Hempstead JL, Morgan JI. Monoclonal antibodies to the rat olfactory sustentacular cell. Brain Res. 1983 Dec 12;288(1-2):289–295. [PubMed]
  • Dexter TM, Spooncer E. Growth and differentiation in the hemopoietic system. Annu Rev Cell Biol. 1987;3:423–441. [PubMed]
  • Lajtha LG. Stem cell concepts. Differentiation. 1979;14(1-2):23–34. [PubMed]
  • Hall PA, Watt FM. Stem cells: the generation and maintenance of cellular diversity. Development. 1989 Aug;106(4):619–633. [PubMed]
  • Potten CS, Loeffler M. Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. Development. 1990 Dec;110(4):1001–1020. [PubMed]
  • Spooncer E, Lord BI, Dexter TM. Defective ability to self-renew in vitro of highly purified primitive haematopoietic cells. Nature. 1985 Jul 4;316(6023):62–64. [PubMed]
  • Jordan CT, McKearn JP, Lemischka IR. Cellular and developmental properties of fetal hematopoietic stem cells. Cell. 1990 Jun 15;61(6):953–963. [PubMed]
  • Jones PH, Watt FM. Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression. Cell. 1993 May 21;73(4):713–724. [PubMed]
  • Deryugina EI, Müller-Sieburg CE. Stromal cells in long-term cultures: keys to the elucidation of hematopoietic development? Crit Rev Immunol. 1993;13(2):115–150. [PubMed]
  • Masui T. Differentiation of the yolk-sac endoderm under the influence of the digestive-tract mesenchyme. J Embryol Exp Morphol. 1981 Apr;62:277–289. [PubMed]
  • Howlett AR, Hodges GM, Rowlatt C. Epithelial-stromal interactions in the adult bladder: urothelial growth, differentiation, and maturation on culture facsimiles of bladder stroma. Dev Biol. 1986 Dec;118(2):403–415. [PubMed]
  • Reh TA, Tully T. Regulation of tyrosine hydroxylase-containing amacrine cell number in larval frog retina. Dev Biol. 1986 Apr;114(2):463–469. [PubMed]
  • Reh TA. Cell-specific regulation of neuronal production in the larval frog retina. J Neurosci. 1987 Oct;7(10):3317–3324. [PubMed]
  • Shah NM, Marchionni MA, Isaacs I, Stroobant P, Anderson DJ. Glial growth factor restricts mammalian neural crest stem cells to a glial fate. Cell. 1994 May 6;77(3):349–360. [PubMed]
  • Kauffman SL. Lengthening of the generation cycle during embryonic differentiation of the mouse neural tube. Exp Cell Res. 1968 Feb;49(2):420–424. [PubMed]

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