Skip to main content

Advertisement

SpringerLink
Log in

Transcriptional Regulation of Neurogenesis in the Olfactory Epithelium

  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

1. The olfactory epithelium (OE) is a simple structure that gives rise to olfactory sensory neurons (OSNs) throughout life.

2. Numerous transcription factors (TFs) are expressed in regions of the OE which contain progenitor cells and OSNs. The function of some of these TFs in OSN development has been elucidated with the aide of transgenic knockout mice.

3. We review here the current state of knowledge on the role of TFs in OE neurogenesis and relate the expression of these TFs, where possible, to the well-documented phenotype of the cells as they progress through the OSN lineage from progenitor cells to mature neurons.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.

Similar content being viewed by others

Abbreviations

ACIII:

adenylyl cyclase III

Atf5:

activating transcription factor 5

BrdU:

bromodeoxyuridine

Dlx5:

Distal-less homeobox homolog 5

E:

embryonic day

GAP43:

43 kDa growth associated protein

GBCs:

globose basal cells

Golf:

olfactory G protein

HBCs:

horizontal basal cells

Hes:

mammalian homolog of hairy and Enhancer of split

HLH:

helix–loop–helix

Id:

inhibitor of DNA binding

INPs:

immediate neuronal precursors

KLF7:

Krüppel-like factor 7

Lhx2:

LIM homeobox protein 2

Mash1:

mammalian achaete-scute homolog 1

Mecp2:

methyl-CpG binding protein 2

Msx1:

msh (muscle specific homeobox) homolog 1

NCAM:

neural cell adhesion molecule

NeuroD:

Neurogenic differentiation

NFI:

nuclear factor I

Ngn:

Neurogenin

OBs:

olfactory bulbs

OcNc:

olfactory cyclic nucleotide-gated channel

OE:

olfactory epithelium

O/E:

Olf (olfactory neuronal transcription factor)/Ebf (early B cell transcription factor)

OMP:

olfactory marker protein

OP:

olfactory placode

ORs:

odorant receptors

OSNs:

olfactory sensory neurons

Otx:

vertebrate homeobox gene related to orthodenticle (otd)

Pax6:

Paired homeobox gene 6

Roaz:

rat O/E-1-associated zinc finger

Runx1:

runt-related transcription factor 1

TFs:

transcription factors

Wt1:

Wilms' tumor gene.

REFERENCES

  • Acampora, D., Mazan, S., Lallemand, Y., Avantaggiato, V., Maury, M., Simeone, A., and Brûlet, P. (1995). Forebrain and midbrain regions are deleted in Otx2-/- mutants due to a defective anterior neuroectoderm specification during gastrulation. Development 121:3279–3290.

    Google Scholar 

  • Ahmad, I., Acharya, H. R., Rogers, J. A., Shibata, A., Smithgall, T. E., and Dooley, C. M. (1998). The role of NeuroD as a differentiation factor in the mammalian retina. J. Mol. Neurosci. 11:165–178.

    Article  Google Scholar 

  • Amir, R. E., Van den Veyver, I. B., Wan, M., Tran, C. Q., Francke, U., and Zoghbi, H. Y. (1999). Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat. Genet. 23:185–188.

    Article  CAS  Google Scholar 

  • Angelastro, J. M., Ignatova, T. N., Kukekov, V. G., Steindler, D. A., Stengren, G. B., Mendelsohn, C., and Greene, L. A. (2003). Regulated expression of ATF5 is required for the progression of neural progenitor cells to neurons. J. Neurosci. 23:4590–4600.

    Google Scholar 

  • Bae, S.-K., Bessho, Y., Hojo, M., and Kageyama, R. (2000). The bHLH gene Hes6, an inhibitor of Hes1, promotes neuronal differentiation. Development 127:2933–2943.

    Google Scholar 

  • Bakalyar, H. A., and Reed, R. R. (1990). Identification of a specialized adenylyl cyclase that may mediate odorant detection. Science 250:1403–1406.

    Article  Google Scholar 

  • Baumeister, H., Gronostajski, R. M., Lyons, G. E., and Margolis, F. L. (1999). Identification of NFI-binding sites and cloning of NFI-cDNAs suggest a regulatory role for NFI transcription factors in olfactory neuron gene expression. Mol. Brain Res. 72:65–79.

    Article  Google Scholar 

  • Behrens, M., Venkatraman, G., Gronostajski, R. M., Reed, R. R., and Margolis, F. L. (2000). NFI in the development of the olfactory neuroepithelium and the regulation of olfactory marker protein gene expression. Eur. J. Neurosci. 12:1372–1384.

    Article  Google Scholar 

  • Belluscio, L., Gold, G. H., Nemes, A., and Axel, R. (1998). Mice deficient in Golf are anosmic. Neuron 20:69–81.

    Article  Google Scholar 

  • Besnard, V., Wert, S. E., Hull, W. M., and Whitsett, J. A. (2004). Immunohistochemical localization of Foxa1 and Foxa2 in mouse embryos and adult tissues. Gene Expr. Patterns 5:193–208.

    Article  CAS  Google Scholar 

  • Briata, P., Di Blas, E., Gulisano, M., Mallamaci, A., Iannone, R., Boncinelli, E., and Corte, G. (1996). EMX1 homeoprotein is expressed in cell nuclei of the developing cerebral cortex and in the axons of the olfactory sensory neurons. Mech. Dev. 57:169–180.

    Article  Google Scholar 

  • Brunet, L. J., Gold, G. H., and Ngai, J. (1996). General anosmia caused by a targeted disruption of the mouse olfactory cyclic nucleotide-gated cation channel. Neuron 17:681–693.

    Article  Google Scholar 

  • 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  Google Scholar 

  • Calof, A. L., Bonnin, A., Crocker, C., Kawauchi, S., Murray, R. C., Shou, J., and Wu, H.-H. (2002). Progenitor cells of the olfactory receptor neuron lineage. Microsc. Res. Technol. 58:176–188.

    Article  CAS  Google Scholar 

  • 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  Google Scholar 

  • Calof, A. L., Hagiwara, N., Holcomb, J. D., Mumm, J. S., and Shou, J. (1996). Neurogenesis and cell death in olfactory epithelium. J. Neurobiol. 30:67–81.

    Article  Google Scholar 

  • Carter, L. A., MacDonald, J. L., and Roskams, A. J. (2004). Olfactory horizontal basal cells demonstrate a conserved multipotent progenitor phenotype. J. Neurosci. 24:5670–5683.

    Article  CAS  Google Scholar 

  • 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.

    Google Scholar 

  • 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.

    Google Scholar 

  • 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.

    Google Scholar 

  • Cohen, D. R. S., Matarazzo, V., Palmer, A. M., Tu, Y., Jeon, O.-H., Pevsner, J., and Ronnett, G. V. (2003). Expression of MeCP2 in olfactory receptor neurons is developmentally regulated and occurs before synaptogenesis. Mol. Cell. Neurosci. 22:417–429.

    Article  CAS  Google Scholar 

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

    Google Scholar 

  • Davis, J. A., and Reed, R. R. (1996). Role of Olf-1 and Pax-6 transcription factors in neurodevelopment. J. Neurosci. 16:5082–5094.

    Google Scholar 

  • de Lorenzo, A. J. (1957). Electron microscope observations of the olfactory mucosa and olfactory nerve. J. Biophys. Biochem. Cytol. 3:839–850.

    Article  Google Scholar 

  • Depew, M. J., Liu, J. K., Long, J. E., Presley, R., Meneses, J. J., Pedersen, R. A., and Rubenstein, J. L. R. (1999). Dlx5 regulates regional development of the brachial arches and sensory capsules. Development 126:3831–3846.

    Google Scholar 

  • Frisch, D. (1967). Ultrastructure of mouse olfactory mucosa. Am. J. Anat. 121:87–120.

    Article  Google Scholar 

  • Ghanbari, H. A., Ghanbari, K., Harris, P. L. R., Jones, P. K., Kubat, Z., Castellani, R. J., Wolozin, B. L., Smith, M. A., and Perry, G. (2004). Oxidative damage in cultured human olfactory neurons from Alzheimer's disease patients. Aging Cell 3:41–44.

    Article  CAS  Google Scholar 

  • 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  Google Scholar 

  • 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  Google Scholar 

  • Grindley, J. C., Davidson, D. R., and Hill, R. E. (1995). The role of Pax-6 in eye and nasal development. Development 121:1433–1442.

    Google Scholar 

  • 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  Google Scholar 

  • Hahn, C.-G., Han, L.-Y., Rawson, N. E., Mirza, N., Borgmann-Winter, K., Lenox, R. H., and Arnold, S. E. (2005). In vivo and in vitro neurogenesis in human olfactory epithelium. J. Comp. Neurol. 483:154–163.

    Article  Google Scholar 

  • Hansen, M. B., Mitchelmore, C., Kjærulff, K. M., Rasmussen, T. E., Pedersen, K. M., and Jensen, N. A. (2002). Mouse Atf5: Molecular cloning of two novel mRNAs, genomic organization, and odorant sensory neuron localization. Genomics 80:344–350.

    Article  CAS  Google Scholar 

  • Hirota, J., and Mombaerts, P. (2004). The LIM-homeodomain protein Lhx2 is required for complete development of mouse olfactory sensory neurons. Proc. Natl. Acad. Sci. U.S.A. 101:8751–8755.

    Article  Google Scholar 

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

    Article  Google Scholar 

  • Horike, S., Cai, S., Miyano, M., Cheng, J.-F., and Kohwi-Shigematsu, T. (2005). Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome. Nat. Genet. 37:31–40.

    Article  CAS  Google Scholar 

  • Iwema, C. L., and Schwob, J. E. (2003). Odorant receptor expression as a function of neuronal maturity in the adult rodent olfactory system. J. Comp. Neurol. 459:209–222.

    Article  CAS  Google Scholar 

  • Jen, Y., Manova, K., and Benezra, R. (1996). Expression patterns of Id1, Id2, and Id3 are highly related but distinct from that of Id4 during mouse embryogenesis. Dev. Dyn. 207:235–252.

    Article  Google Scholar 

  • Jones, D. T., and Reed, R. R. (1989). Golf: An olfactory neuron specific-G protein involved in odorant signal transduction. Science 244:790–795.

    Article  Google Scholar 

  • Kolterud, Å., Alenius, M., Carlsson, L., and Bohm, S. (2004). The Lim homeobox gene Lhx2 is required for olfactory sensory neuron identity. Development 131:5319–5326.

    Article  CAS  Google Scholar 

  • Koyano-Nakagawa, N., Kim, J., Anderson, D., and Kintner, C. (2000). Hes6 acts in a positive feedback loop with the neurogenins to promote neuronal differentiation. Development 127:4203–4216.

    Google Scholar 

  • Kudrycki, K. E., Buiakova, O., Tarozzo, G., Grillo, M., Walters, E., and Margolis, F. L. (1998). Effects of mutation of the Olf-1 motif on transgene expression in olfactory receptor neurons. J. Neurosci. Res. 52:159–172.

    Article  Google Scholar 

  • Kudrycki, K., Stein-Izsak, C., Behn, C., Grillo, M., Akeson, R., and Margolis, F. L. (1993). Olf-1-binding site: Characterization of an olfactory neuron-specific promoter motif. Mol. Cell. Biol. 13:3002–3014.

    Google Scholar 

  • Laub, F., Aldabe, R., Friedrich, V., Jr., Ohnishi, S., Yoshida, T., and Ramirez, F. (2001). Developmental expression of mouse Kruppel-like transcription factor KLF7 suggests a potential role in neurogenesis. Dev. Biol. 233:305–318.

    Article  CAS  Google Scholar 

  • Laub, F., Lei, L., Sumiyoshi, H., Kajimura, D., Dragomir, C., Smaldone, S., Puche, A. C., Petros, T. J., Mason, C., Parada, L. F., and Ramirez, F. (2005). Transcription factor KLF7 is important for neuronal morphogenesis in selected regions of the nervous system. Mol. Cell. Biol. 25:5699–5711.

    Article  CAS  Google Scholar 

  • Lee, S. S. J., Wan, M., and Francke, U. (2001). Spectrum of MECP2 mutations in Rett syndrome. Brain Dev. 23:S138–S143.

    Article  PubMed  Google Scholar 

  • Leid, M., Ishmael, J. E., Avram, D., Shepherd, D., Fraulob, V., and Dollé, P. (2004). CTIP1 and CTIP2 are differentially expressed during mouse embryogenesis. Gene Exp. Patterns 4:733–739.

    Article  CAS  Google Scholar 

  • Levi, G., Puche, A. C., Mantero, S., Barbieri, O., Trombino, S., Paleari, L., Egeo, A., and Merlo, G. R. (2003). The Dlx5 homeodomain gene is essential for olfactory development and connectivity in the mouse. Mol. Cell. Neurosci. 22:530–543.

    Article  CAS  Google Scholar 

  • Lin, H., and Grosschedl, R. (1995). Failure of B-cell differentiation in mice lacking the transcription factor EBF. Nature 376:263–267.

    Article  Google Scholar 

  • Long, J. E., Garel, S., Depew, M. J., Tobet, S., and Rubenstein, J. L. R. (2003). DLX5 regulates development of peripheral and central components of the olfactory system. J. Neurosci. 23:568–578.

    Google Scholar 

  • Lu, Q. R., Sun, T., Zhu, Z., Ma, N., Garcia, M., Stiles, C. D., and Rowitch, D. H. (2002). Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection. Cell 109:75–86.

    Article  Google Scholar 

  • Luo, Y., Hurwitz, J., and Massagué, J. (1995). Cell-cycle inhibition by independent CDK and PCNA binding domains in p21Cip1. Nature 375:159–161.

    Article  Google Scholar 

  • Lyden, D., Young, A. Z., Zagzag, D., Yan, W., Gerald, W., O'Reilly, R., Bader, B. L., Hynes, R. O., Zhuang, Y., Manova, K., and Benezra, R. (1999). Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts. Nature 401:670–677.

    Article  Google Scholar 

  • Malgaretti, N., Pozzoli, O., Bosetti, A., Corradi, A., Ciarmatori, S., Panigada, M., Bianchi, M. E., Martinez, S., and Consalez, G. G. (1997). Mmot1, a new helix-loop-helix transcription factor gene displaying a sharp expression boundary in the embryonic mouse brain. J. Biol. Chem. 272:17632–17639.

    Article  Google Scholar 

  • Mallamaci, A., Di Blas, E., Briata, P., Boncinelli, E., and Corte, G. (1996). OTX2 homeoprotein in the developing central nervous system and migratory cells of the olfactory area. Mech. Dev. 58:165–178.

    Article  Google Scholar 

  • Mallamaci, A., Iannone, R., Briata, P., Pintonello, L., Mercurio, S., Boncinelli, E., and Corte, G. (1998). EMX2 protein in the developing mouse brain and olfactory area. Mech. Dev. 77:165–172.

    Article  Google Scholar 

  • Malnic, B., Hirono, J., Sato, T., and Buck, L. B. (1999). Combinatorial receptor codes for odors. Cell 96:713–723.

    Article  Google Scholar 

  • Manglapus, G. L., Youngentob, S. L., and Schwob, J. E. (2004). Expression patterns of basic helix-loop-helix transcription factors define subsets of olfactory progenitor cells. J. Comp. Neurol. 479:216–233.

    Article  CAS  Google Scholar 

  • Matarazzo, V., Cohen, D., Palmer, A. M., Simpson, P. J., Khokhar, B., Pan, S.-J., and Ronnett, G. V. (2004). The transcriptional repressor Mecp2 regulates terminal neuronal differentiation. Mol. Cell. Neurosci. 27:44–58.

    Article  CAS  Google Scholar 

  • Matsuzaki, O., Bakin, R. E., Cai, X., Menco, B. P. M., and Ronnett, G. V. (1999). Localization of the olfactory cyclic nucleotide-gated channel subunit 1 in normal, embryonic and regenerating olfactory epithelium. Neuroscience 94:131–140.

    Article  Google Scholar 

  • Mombaerts, P., Wang, F., Dulac, C., Chao, S. K., Nemes, A., Mendelsohn, M., Edmondson, J., and Axel, R. (1996). Visualizing an olfactory sensory map. Cell 87:675–686.

    Article  Google Scholar 

  • Morrison, E., and Costanzo, R. (1992). Morphology of olfactory epithelium in humans and other vertebrates. Microsc. Res. Technol. 23:49–61.

    Article  Google Scholar 

  • 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.

    Google Scholar 

  • Nédélec, S., Foucher, I., Brunet, I., Bouillot, C., Prochiantz, A., and Trembleau, A. (2004). Emx2 homeodomain transcription factor interacts with eukaryotic translation initiation factor 4E (eIF4E) in the axons of olfactory sensory neurons. Proc. Natl. Acad. Sci. U.S.A. 101:10815–10820.

    Article  Google Scholar 

  • Nishimura, M., Isaka, F., Ishibashi, M., Tomita, K., Tsuda, H., Nakanishi, S., and Kageyama, R. (1998). Structure, chromosomal locus, and promoter of mouse Hes2 gene, a homologue of Drosophila hairy and Enhancer of split. Genomics 49:69–75.

    Article  Google Scholar 

  • Norlin, E. M., Alenius, M., Gussing, F., Hägglund, M., Vedin, V., and Bohm, S. (2001). Evidence for gradients of gene expression correlating with zonal topography of the olfactory sensory map. Mol. Cell. Neurosci. 18:283–295.

    Article  CAS  Google Scholar 

  • Pellier-Monnin, V., Astic, L., Bichet, S., Riederer, B. M., and Grenningloh, G. (2001). Expression of SCG10 and stathmin proteins in the rat olfactory system during development and axonal regeneration. J. Comp. Neurol. 433:239–254.

    Article  Google Scholar 

  • Ronnett, G. V., and Moon, C. (2002). G proteins and olfactory signal transduction. Ann. Rev. Physiol. 64:189–222.

    Article  Google Scholar 

  • Ronnett, G. V., Leopold, D., Cai, X., Hoffbuhr, K. C., Moses, L., Hoffman, E. P., and Naidu, S. (2003). Olfactory biopsies demonstrate a defect in neuronal development in Rett's syndrome. Ann. Neurol. 54:206–218.

    Article  CAS  Google Scholar 

  • Roskams, A. J. I., Cai, X., and Ronnett, G. V. (1998). Expression of neuron-specific beta-III tubulin during olfactory neurogenesis in the embryonic and adult rat. Neurosci. 83:191–200.

    Article  Google Scholar 

  • Saito, T., Lo, L., Anderson, D. J., and Mikoshiba, K. (1996). Identification of novel paired homeodomain protein related to C. elegans unc-4 as a potential downstream target of MASH1. Dev. Biol. 180:143–155.

    Article  Google Scholar 

  • 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. 11:3556–3564.

    Google Scholar 

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

    Article  Google Scholar 

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

    Google Scholar 

  • 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  Google Scholar 

  • Simeone, A., Acampora, D., Mallamaci, A., Stornaiuolo, A., D'Apice, M. R., Nigro, V., and Boncinelli, E. (1993). A vertebrate gene related to orthodenticle contains a homeodomain of the bicoid class and demarcates anterior neuroectoderm in the gastrulating mouse embryo. EMBO J. 12:2735–2747.

    Google Scholar 

  • Smart, I. H. M. (1971). Location and orientation of mitotic figures in the developing mouse olfactory epithelium. J. Anat. 109:243–251.

    Google Scholar 

  • Sullivan, S. L., Bohm, S., Ressler, K. J., Horowitz, L. F., and Buck, L. B. (1995). Target-independent pattern specification in the olfactory epithelium. Neuron 15:779–789.

    Article  Google Scholar 

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

    Article  Google Scholar 

  • Suzuki, Y., Tsuruga, E., Yajima, T., and Takeda, M. (2003b). Expression of bHLH transcription factors NSCL1 and NSCL2 in the mouse olfactory system. Chem. Senses 28:603–608.

    Article  CAS  Google Scholar 

  • Takebayashi, H., Yoshida, S., Sugimori, M., Kosako, H., Kominami, R., Nakafuku, M., and Nabeshima, Y. (2000). Dynamic expression of basic helix-loop-helix Olig family members: Implication of Olig2 in neuron and oligodendrocyte differentiation and identification of a new member, Olig3. Mech. Dev. 99:143–148.

    Article  Google Scholar 

  • Tanaka, H., Yamashita, T., Asada, M., Mizutani, S., Yoshikawa, H., and Tohyama, M. (2002). Cytoplasmic p21Cip1/WAF1 regulates neurite remodeling by inhibiting Rho-kinase activity. J. Cell Biol. 158:321–329.

    Article  CAS  Google Scholar 

  • Tao, W., and Lai, E. (1992). Telencephalon-restricted expression of BF-1, a new member of the HNF-3/fork head gene family, in the developing rat brain. Neuron 8:957–966.

    Article  Google Scholar 

  • Theriault, F. M., Nuthall, H. N., Dong, Z., Lo, R., Barnabe-Heider, F., Miller, F. D., and Stifani, S. (2005). Role for Runx1 in the proliferation and neuronal differentiation of selected progenitor cells in the mammalian nervous system. J. Neurosci. 25:2050–2061.

    Article  CAS  Google Scholar 

  • Tietjen, I., Rihel, J. M., Cao, Y., Koentges, G., Zakhary, L., and Dulac, C. (2003). Single-cell transcriptional analysis of neuronal progenitors. Neuron 38:161–175.

    Article  Google Scholar 

  • Tsai, R. Y. L., and Reed, R. R. (1997). Cloning and functional characterization of Roaz, a zinc finger protein that interacts with O/E-1 to regulate gene expression: implications for olfactory neuronal development. J. Neurosci. 17:4159–4169.

    Google Scholar 

  • 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.

    Google Scholar 

  • Wagner, N., Wagner, K.-D., Hammes, A., Kirschner, K. M., Vidal, V. P., Schedl, A., and Scholz, H. (2005). A splice variant of the Wilms' tumour suppressor Wt1 is required for normal development of the olfactory system. Development 132:1327–1336.

    Article  CAS  Google Scholar 

  • Wang, M. M., Tsai, R. Y. L., Schrader, K. A., and Reed, R. R. (1993). Genes encoding components of the olfactory signal transduction cascade contain a DNA binding site that may direct neuronal expression. Mol. Cell Biol. 13:5805–5813.

    Google Scholar 

  • Wang, S. S., Betz, A. G., and Reed, R. R. (2002). Cloning of a novel Olf-1/EBF-like gene, O/E-4, by degenerate oligo-based direct selection. Mol. Cell. Neurosci. 20:404–414.

    Article  CAS  Google Scholar 

  • Wang, S. S., Lewcock, J. W., Feinstein, P., Mombaerts, P., and Reed, R. R. (2004). Genetic disruptions of O/E2 and O/E3 genes reveal involvement in olfactory receptor neuron projection. Development 131:1377–1388.

    Article  CAS  Google Scholar 

  • Wang, S. S., Tsai, R. Y. L., and Reed, R. R. (1997). The characterization of the Olf-1/EBF-like HLH transcription factor family: Implications in olfactory gene regulation and neuronal development. J. Neurosci. 17:4149–4158.

    Google Scholar 

  • Whitesides, J. G., III, and LaMantia, A.-S. (1996). Differential adhesion and the initial assembly of the mammalian olfactory nerve. J. Comp. Neurol. 373:240–254.

    Article  Google Scholar 

  • Wong, S. T., Trinh, K., Hacker, B., Chan, G. C. K., Lowe, G., Gaggar, A. Xia, Z., Gold, G. H., and Storm, D. R. (2000). Disruption of the type III adenylyl cyclase gene leads to peripheral ad behavioral anosmia in transgenic mice. Neuron 27:487–497.

    Article  Google Scholar 

  • Yoshida, M., Suda, Y., Matsuo, I., Miyamoto, N., Takeda, N., Kuratani, S., and Aizawa, S. (1997). Emx1 and Emx2 functions in development of dorsal telencephalon. Development 124:101–111.

    Google Scholar 

  • Zhang, X., and Firestein, S. (2002). The olfactory receptor gene superfamily of the mouse. Nat. Neurosci. 5:124–133.

    Google Scholar 

Download references

ACKNOWLEDGMENTS

Supported by a research grant from the Canadian Institutes of Health Research (CIHR) and the Multiple Sclerosis Society of Canada to AJN and JRD. DJN is supported by a CIHR Health Research Fellowship

Author information

Authors and Affiliations

  1. Laboratory of Molecular Biology, College of Pharmacy and Nutrition, University of Saskatchewan, 116 Thorvaldson Building, 110 Science Place, Saskatoon, Saskatchewan, Canada S7N 5C9

    Danette J. Nicolay & Adil J. Nazarali

  2. Department of Anatomy and Cell Biology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

    J. Ronald Doucette

  3. Cameco MS Neuroscience Research Center, City Hospital, Saskatoon, Saskatchewan, Canada

    J. Ronald Doucette & Adil J. Nazarali

Authors
  1. Danette J. Nicolay
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Ronald Doucette
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Adil J. Nazarali
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Adil J. Nazarali.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nicolay, D.J., Doucette, J.R. & Nazarali, A.J. Transcriptional Regulation of Neurogenesis in the Olfactory Epithelium. Cell Mol Neurobiol 26, 801–819 (2006). https://doi.org/10.1007/s10571-006-9058-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-006-9058-4

KEY WORDS:

Search

Navigation