Molecular Neurobiology

, Volume 55, Issue 11, pp 8306–8327 | Cite as

Transcriptional and Epigenetic Control of Mammalian Olfactory Epithelium Development

  • Godwin Sokpor
  • Eman Abbas
  • Joachim Rosenbusch
  • Jochen F. Staiger
  • Tran TuocEmail author


The postnatal mammalian olfactory epithelium (OE) represents a major aspect of the peripheral olfactory system. It is a pseudostratified tissue that originates from the olfactory placode and is composed of diverse cells, some of which are specialized receptor neurons capable of transducing odorant stimuli to afford the perception of smell (olfaction). The OE is known to offer a tractable miniature model for studying the systematic generation of neurons and glia that typify neural tissue development. During OE development, stem/progenitor cells that will become olfactory sensory neurons and/or non-neuronal cell types display fine spatiotemporal expression of neuronal and non-neuronal genes that ensures their proper proliferation, differentiation, survival, and regeneration. Many factors, including transcription and epigenetic factors, have been identified as key regulators of the expression of such requisite genes to permit normal OE morphogenesis. Typically, specific interactive regulatory networks established between transcription and epigenetic factors/cofactors orchestrate histogenesis in the embryonic and adult OE. Hence, investigation of these regulatory networks critical for OE development promises to disclose strategies that may be employed in manipulating the stepwise transition of olfactory precursor cells to become fully differentiated and functional neuronal and non-neuronal cell types. Such strategies potentially offer formidable means of replacing injured or degenerated neural cells as therapeutics for nervous system perturbations. This review recapitulates the developmental cellular diversity of the olfactory neuroepithelium and discusses findings on how the precise and cooperative molecular control by transcriptional and epigenetic machinery is indispensable for OE ontogeny.


Olfactory epithelium Olfactory neural stem cell Neurogenesis Transcription factor Chromatin remodeling factor Epigenetic factor 



We apologize to colleagues whose work was not cited due to unintentional oversight. We thank H. Sebesse for preparing illustrations. This work was supported by the Research Program at the Faculty of Medicine, Georg-August University Göttingen, TU432/1-1, TU432/1-3 DFG grants, DFG-CNMPB, and Schram-Stiftung to TT. The authors declare no competing financial interests.

Author Contributions

GS, EA, JFS, and TT all contributed to writing and editing the manuscript.


  1. 1.
    Frisch D (1967) Ultrastructure of mouse olfactory mucosa. Am J Anat 121(1):87–120PubMedGoogle Scholar
  2. 2.
    Morrison EE, Costanzo RM (1992) Morphology of olfactory epithelium in humans and other vertebrates. Microsc Res Tech 23(1):49–61PubMedGoogle Scholar
  3. 3.
    Schwob JE (2002) Neural regeneration and the peripheral olfactory system. Anat Rec 269(1):33–49PubMedGoogle Scholar
  4. 4.
    Cuschieri A, Bannister LH (1975) The development of the olfactory mucosa in the mouse: light microscopy. J Anat 119(Pt 2):277–286PubMedPubMedCentralGoogle Scholar
  5. 5.
    Beites CL et al (2005) Identification and molecular regulation of neural stem cells in the olfactory epithelium. Exp Cell Res 306(2):309–316PubMedGoogle Scholar
  6. 6.
    Cau E, Casarosa S, Guillemot F (2002) Mash1 and Ngn1 control distinct steps of determination and differentiation in the olfactory sensory neuron lineage. Development 129(8):1871–1880PubMedGoogle Scholar
  7. 7.
    Graziadei PP, Graziadei GA (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):1–18PubMedGoogle Scholar
  8. 8.
    Schnittke N et al (2015) Transcription factor p63 controls the reserve status but not the stemness of horizontal basal cells in the olfactory epithelium. Proc Natl Acad Sci U S A 112(36):E5068–E5077PubMedPubMedCentralGoogle Scholar
  9. 9.
    Suzuki J et al (2015) horizontal basal cell-specific deletion of Pax6 impedes recovery of the olfactory neuroepithelium following severe injury. Stem Cells Dev 24(16):1923–1933PubMedPubMedCentralGoogle Scholar
  10. 10.
    Weng PL, Vinjamuri M, Ovitt CE (2016) Ascl3 transcription factor marks a distinct progenitor lineage for non-neuronal support cells in the olfactory epithelium. Sci Rep 6:38199PubMedPubMedCentralGoogle Scholar
  11. 11.
    Schwob JE et al (2017) Stem and progenitor cells of the mammalian olfactory epithelium: taking poietic license. J Comp Neurol 525(4):1034–1054PubMedGoogle Scholar
  12. 12.
    Murdoch B, Roskams AJ (2007) Olfactory epithelium progenitors: insights from transgenic mice and in vitro biology. J Mol Histol 38(6):581–599PubMedGoogle Scholar
  13. 13.
    Kam JW, Raja R, Cloutier JF (2014) Cellular and molecular mechanisms regulating embryonic neurogenesis in the rodent olfactory epithelium. Int J Dev Neurosci 37:76–86PubMedGoogle Scholar
  14. 14.
    Nicolay DJ, Doucette JR, Nazarali AJ (2006) Transcriptional regulation of neurogenesis in the olfactory epithelium. Cell Mol Neurobiol 26(4-6):803–821PubMedGoogle Scholar
  15. 15.
    Sokpor G et al (2017) Chromatin remodeling BAF (SWI/SNF) complexes in neural development and disorders. Front Mol Neurosci 10:243PubMedPubMedCentralGoogle Scholar
  16. 16.
    Bachmann C et al (2016) mSWI/SNF (BAF) complexes are indispensable for the neurogenesis and development of embryonic olfactory epithelium. PLoS Genet 12(9):e1006274PubMedPubMedCentralGoogle Scholar
  17. 17.
    Choi PS et al (2008) Members of the miRNA-200 family regulate olfactory neurogenesis. Neuron 57(1):41–55PubMedPubMedCentralGoogle Scholar
  18. 18.
    Goldstein BJ et al (2016) Contribution of polycomb group proteins to olfactory basal stem cell self-renewal in a novel c-KIT+ culture model and in vivo. Development 143(23):4394–4404PubMedPubMedCentralGoogle Scholar
  19. 19.
    Suzuki, J. and N. Osumi, Chapter Ten - Neural Crest and Placode Contributions to Olfactory Development, in Current Topics in Developmental Biology, P.A. Trainor, Editor. 2015, Academic Press. p. 351-374.Google Scholar
  20. 20.
    Cowan CM, Roskams AJ (2004) Caspase-3 and caspase-9 mediate developmental apoptosis in the mouse olfactory system. J Comp Neurol 474(1):136–148PubMedGoogle Scholar
  21. 21.
    Calof AL, Chikaraishi DM (1989) Analysis of neurogenesis in a mammalian neuroepithelium: proliferation and differentiation of an olfactory neuron precursor in vitro. Neuron 3(1):115–127PubMedGoogle Scholar
  22. 22.
    Mackay-Sim A, Kittel P (1991) Cell dynamics in the adult mouse olfactory epithelium: a quantitative autoradiographic study. J Neurosci 11(4):979–984PubMedGoogle Scholar
  23. 23.
    Holbrook EH, Szumowski KE, Schwob JE (1995) An immunochemical, ultrastructural, and developmental characterization of the horizontal basal cells of rat olfactory epithelium. J Comp Neurol 363(1):129–146PubMedGoogle Scholar
  24. 24.
    Sansom SN et al (2009) The level of the transcription factor Pax6 is essential for controlling the balance between neural stem cell self-renewal and neurogenesis. PLoS Genet 5(6):e1000511PubMedPubMedCentralGoogle Scholar
  25. 25.
    Guo Z et al (2010) Expression of pax6 and sox2 in adult olfactory epithelium. J Comp Neurol 518(21):4395–4418PubMedPubMedCentralGoogle Scholar
  26. 26.
    Joiner AM et al (2015) Primary cilia on horizontal basal cells regulate regeneration of the olfactory epithelium. J Neurosci 35(40):13761–13772PubMedPubMedCentralGoogle Scholar
  27. 27.
    Carter LA, MacDonald JL, Roskams AJ (2004) Olfactory horizontal basal cells demonstrate a conserved multipotent progenitor phenotype. J Neurosci 24(25):5670–5683PubMedGoogle Scholar
  28. 28.
    Leung CT, Coulombe PA, Reed RR (2007) Contribution of olfactory neural stem cells to tissue maintenance and regeneration. Nat Neurosci 10(6):720–726PubMedGoogle Scholar
  29. 29.
    Iwai N et al (2008) Horizontal basal cells are multipotent progenitors in normal and injured adult olfactory epithelium. Stem Cells 26(5):1298–1306PubMedPubMedCentralGoogle Scholar
  30. 30.
    Suzuki J et al (2013) Neural crest-derived horizontal basal cells as tissue stem cells in the adult olfactory epithelium. Neurosci Res 75(2):112–120PubMedGoogle Scholar
  31. 31.
    Huard JM et al (1998) Adult olfactory epithelium contains multipotent progenitors that give rise to neurons and non-neural cells. J Comp Neurol 400(4):469–486PubMedGoogle Scholar
  32. 32.
    Schwob JE, Youngentob SL, Mezza RC (1995) Reconstitution of the rat olfactory epithelium after methyl bromide-induced lesion. J Comp Neurol 359(1):15–37PubMedGoogle Scholar
  33. 33.
    Caggiano M, Kauer JS, Hunter DD (1994) Globose basal cells are neuronal progenitors in the olfactory epithelium: a lineage analysis using a replication-incompetent retrovirus. Neuron 13(2):339–352PubMedGoogle Scholar
  34. 34.
    Schwob JE, Youngentob SL, Meiri KF (1994) On the formation of neuromata in the primary olfactory projection. J Comp Neurol 340(3):361–380PubMedGoogle Scholar
  35. 35.
    Cau E et al (2000) Hes genes regulate sequential stages of neurogenesis in the olfactory epithelium. Development 127(11):2323–2332PubMedGoogle Scholar
  36. 36.
    Manglapus GL, Youngentob SL, Schwob JE (2004) Expression patterns of basic helix-loop-helix transcription factors define subsets of olfactory progenitor cells. J Comp Neurol 479(2):216–233PubMedGoogle Scholar
  37. 37.
    DeHamer MK et al (1994) Genesis of olfactory receptor neurons in vitro: regulation of progenitor cell divisions by fibroblast growth factors. Neuron 13(5):1083–1097PubMedGoogle Scholar
  38. 38.
    Schwob JE (2005) Restoring olfaction: a view from the olfactory epithelium. Chem Senses 30(Suppl 1):i131–i132PubMedGoogle Scholar
  39. 39.
    Goldstein BJ et al (1998) Transplantation of multipotent progenitors from the adult olfactory epithelium. Neuroreport 9(7):1611–1617PubMedGoogle Scholar
  40. 40.
    Chen X, Fang H, Schwob JE (2004) Multipotency of purified, transplanted globose basal cells in olfactory epithelium. J Comp Neurol 469(4):457–474PubMedGoogle Scholar
  41. 41.
    Gordon MK et al (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(4):363–379PubMedGoogle Scholar
  42. 42.
    Regad T et al (2007) The neural progenitor-specifying activity of FoxG1 is antagonistically regulated by CKI and FGF. Nat Cell Biol 9(5):531–540PubMedGoogle Scholar
  43. 43.
    Roskams AJ et al (1994) Nitric oxide mediates the formation of synaptic connections in developing and regenerating olfactory receptor neurons. Neuron 13(2):289–299PubMedGoogle Scholar
  44. 44.
    Verhaagen J et al (1989) The expression of the growth associated protein B50/GAP43 in the olfactory system of neonatal and adult rats. J Neurosci 9(2):683–691PubMedGoogle Scholar
  45. 45.
    Pellier-Monnin V et al (2001) Expression of SCG10 and stathmin proteins in the rat olfactory system during development and axonal regeneration. J Comp Neurol 433(2):239–254PubMedGoogle Scholar
  46. 46.
    Ronnett GV, Moon C (2002) G proteins and olfactory signal transduction. Annu Rev Physiol 64:189–222PubMedGoogle Scholar
  47. 47.
    De Lorenzo AJ (1957) Electron microscopic observations of the olfactory mucosa and olfactory nerve. J Biophys Biochem Cytol 3(6):839–850PubMedCentralGoogle Scholar
  48. 48.
    Menco BP (1980) Qualitative and quantitative freeze-fracture studies on olfactory and nasal respiratory epithelial surfaces of frog, ox, rat, and dog. III Tight-junctions. Cell Tissue Res 211(3):361–373PubMedGoogle Scholar
  49. 49.
    Farbman AI, Margolis FL (1980) Olfactory marker protein during ontogeny: immunohistochemical localization. Dev Biol 74(1):205–215PubMedGoogle Scholar
  50. 50.
    Miragall F et al (1994) Expression of the tight junction protein ZO-1 in the olfactory system: presence of ZO-1 on olfactory sensory neurons and glial cells. J Comp Neurol 341(4):433–448PubMedGoogle Scholar
  51. 51.
    Nomura T, Takahashi S, Ushiki T (2004) Cytoarchitecture of the normal rat olfactory epithelium: light and scanning electron microscopic studies. Arch Histol Cytol 67(2):159–170PubMedGoogle Scholar
  52. 52.
    Goldstein BJ, Schwob JE (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(12):4005–4016PubMedGoogle Scholar
  53. 53.
    Chen Y et al (1992) Immunolocalization of two cytochrome P450 isozymes in rat nasal chemosensory tissue. Neuroreport 3(9):749–752PubMedGoogle Scholar
  54. 54.
    Suzuki Y, Schafer J, Farbman AI (1995) Phagocytic cells in the rat olfactory epithelium after bulbectomy. Exp Neurol 136(2):225–233PubMedGoogle Scholar
  55. 55.
    Ding XX, Coon MJ (1988) Purification and characterization of two unique forms of cytochrome P-450 from rabbit nasal microsomes. Biochemistry 27(22):8330–8337PubMedGoogle Scholar
  56. 56.
    Davis JA, Reed RR (1996) Role of Olf-1 and Pax-6 transcription factors in neurodevelopment. J Neurosci 16(16):5082–5094PubMedGoogle Scholar
  57. 57.
    Murray RC et al (2003) Widespread defects in the primary olfactory pathway caused by loss of Mash1 function. J Neurosci 23(5):1769–1780PubMedGoogle Scholar
  58. 58.
    Barraud P et al (2010) Neural crest origin of olfactory ensheathing glia. Proc Natl Acad Sci U S A 107(49):21040–21045PubMedPubMedCentralGoogle Scholar
  59. 59.
    Doucette R (1991) PNS-CNS transitional zone of the first cranial nerve. J Comp Neurol 312(3):451–466PubMedGoogle Scholar
  60. 60.
    Ekberg JA et al (2012) The migration of olfactory ensheathing cells during development and regeneration. Neurosignals 20(3):147–158PubMedGoogle Scholar
  61. 61.
    Windus LC et al (2011) Stimulation of olfactory ensheathing cell motility enhances olfactory axon growth. Cell Mol Life Sci 68(19):3233–3247PubMedGoogle Scholar
  62. 62.
    Windus LC et al (2007) Motile membrane protrusions regulate cell-cell adhesion and migration of olfactory ensheathing glia. Glia 55(16):1708–1719PubMedGoogle Scholar
  63. 63.
    Chehrehasa F et al (2010) Olfactory glia enhance neonatal axon regeneration. Mol Cell Neurosci 45(3):277–288PubMedGoogle Scholar
  64. 64.
    Tennent R, Chuah MI (1996) Ultrastructural study of ensheathing cells in early development of olfactory axons. Brain Res Dev Brain Res 95(1):135–139PubMedGoogle Scholar
  65. 65.
    Au WW, Treloar HB, Greer CA (2002) Sublaminar organization of the mouse olfactory bulb nerve layer. J Comp Neurol 446(1):68–80PubMedGoogle Scholar
  66. 66.
    Baker CV, Bronner-Fraser M (2001) Vertebrate cranial placodes I. Embryonic induction. Dev Biol 232(1):1–61PubMedGoogle Scholar
  67. 67.
    Pixley SK (1992) CNS glial cells support in vitro survival, division, and differentiation of dissociated olfactory neuronal progenitor cells. Neuron 8(6):1191–1204PubMedGoogle Scholar
  68. 68.
    Devon R, Doucette R (1992) Olfactory ensheathing cells myelinate dorsal root ganglion neurites. Brain Res 589(1):175–179PubMedGoogle Scholar
  69. 69.
    Kato T et al (2000) Transplantation of human olfactory ensheathing cells elicits remyelination of demyelinated rat spinal cord. Glia 30(3):209–218PubMedPubMedCentralGoogle Scholar
  70. 70.
    Franklin RJ et al (1996) Schwann cell-like myelination following transplantation of an olfactory bulb-ensheathing cell line into areas of demyelination in the adult CNS. Glia 17(3):217–224PubMedGoogle Scholar
  71. 71.
    Imaizumi T et al (1998) Transplanted olfactory ensheathing cells remyelinate and enhance axonal conduction in the demyelinated dorsal columns of the rat spinal cord. J Neurosci 18(16):6176–6185PubMedPubMedCentralGoogle Scholar
  72. 72.
    Ramon-Cueto A, Valverde F (1995) Olfactory bulb ensheathing glia: a unique cell type with axonal growth-promoting properties. Glia 14(3):163–173PubMedGoogle Scholar
  73. 73.
    Li Y, Field PM, Raisman G (1998) Regeneration of adult rat corticospinal axons induced by transplanted olfactory ensheathing cells. J Neurosci 18(24):10514–10524PubMedGoogle Scholar
  74. 74.
    Roet KC, Verhaagen J (2014) Understanding the neural repair-promoting properties of olfactory ensheathing cells. Exp Neurol 261:594–609PubMedGoogle Scholar
  75. 75.
    Chen CR et al (2014) Anatomy and cellular constituents of the human olfactory mucosa: a review. J Neurol Surg B Skull Base 75(5):293–300PubMedPubMedCentralGoogle Scholar
  76. 76.
    Mellert TK et al (1992) Characterization of the immune barrier in human olfactory mucosa. Otolaryngol Head Neck Surg 106(2):181–188PubMedGoogle Scholar
  77. 77.
    Solbu TT, Holen T (2012) Aquaporin pathways and mucin secretion of Bowman's glands might protect the olfactory mucosa. Chem Senses 37(1):35–46PubMedGoogle Scholar
  78. 78.
    Yu TT et al (2005) Differentially expressed transcripts from phenotypically identified olfactory sensory neurons. J Comp Neurol 483(3):251–262PubMedPubMedCentralGoogle Scholar
  79. 79.
    Moran DT, Rowley JC 3rd, Jafek BW (1982) Electron microscopy of human olfactory epithelium reveals a new cell type: the microvillar cell. Brain Res 253(1-2):39–46PubMedGoogle Scholar
  80. 80.
    Lin W et al (2008) TRPM5-expressing microvillous cells in the main olfactory epithelium. BMC Neurosci 9:114PubMedPubMedCentralGoogle Scholar
  81. 81.
    Pfister S et al (2012) Characterization and turnover of CD73/IP(3)R3-positive microvillar cells in the adult mouse olfactory epithelium. Chem Senses 37(9):859–868PubMedGoogle Scholar
  82. 82.
    Elsaesser R et al (2005) Phosphatidyl-inositide signalling proteins in a novel class of sensory cells in the mammalian olfactory epithelium. Eur J Neurosci 21(10):2692–2700PubMedGoogle Scholar
  83. 83.
    Hansel DE, Eipper BA, Ronnett GV (2001) Neuropeptide Y functions as a neuroproliferative factor. Nature 410(6831):940–944PubMedGoogle Scholar
  84. 84.
    Doyle KL et al (2008) Y1 receptors are critical for the proliferation of adult mouse precursor cells in the olfactory neuroepithelium. J Neurochem 105(3):641–652PubMedGoogle Scholar
  85. 85.
    Cau E et al (1997) Mash1 activates a cascade of bHLH regulators in olfactory neuron progenitors. Development 124(8):1611–1621PubMedGoogle Scholar
  86. 86.
    Donner AL, Episkopou V, Maas RL (2007) Sox2 and Pou2f1 interact to control lens and olfactory placode development. Dev Biol 303(2):784–799PubMedGoogle Scholar
  87. 87.
    Sarkar A, Hochedlinger K (2013) The sox family of transcription factors: versatile regulators of stem and progenitor cell fate. Cell Stem Cell 12(1):15–30PubMedPubMedCentralGoogle Scholar
  88. 88.
    Tucker ES et al (2010) Proliferative and transcriptional identity of distinct classes of neural precursors in the mammalian olfactory epithelium. Development (Cambridge England) 137(15):2471–2481Google Scholar
  89. 89.
    Wegner M, Stolt CC (2005) From stem cells to neurons and glia: a Soxist's view of neural development. Trends Neurosci 28(11):583–588PubMedGoogle Scholar
  90. 90.
    Avilion AA et al (2003) Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev 17(1):126–140PubMedPubMedCentralGoogle Scholar
  91. 91.
    Wang YZ et al (2011) Canonical Wnt signaling promotes the proliferation and neurogenesis of peripheral olfactory stem cells during postnatal development and adult regeneration. J Cell Sci 124(Pt 9):1553–1563PubMedPubMedCentralGoogle Scholar
  92. 92.
    Smart IH (1971) Location and orientation of mitotic figures in the developing mouse olfactory epithelium. J Anat 109(Pt 2):243–251PubMedPubMedCentralGoogle Scholar
  93. 93.
    Walther C, Gruss P (1991) Pax-6, a murine paired box gene, is expressed in the developing CNS. Development 113(4):1435–1449PubMedGoogle Scholar
  94. 94.
    Collinson JM et al (2003) The roles of Pax6 in the cornea, retina, and olfactory epithelium of the developing mouse embryo. Dev Biol 255(2):303–312PubMedGoogle Scholar
  95. 95.
    Osada M et al (1998) Cloning and functional analysis of human p51, which structurally and functionally resembles p53. Nat Med 4(7):839–843PubMedGoogle Scholar
  96. 96.
    Yang A et al (1998) p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol Cell 2(3):305–316PubMedGoogle Scholar
  97. 97.
    Mills AA et al (1999) p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature 398(6729):708–713PubMedGoogle Scholar
  98. 98.
    Packard A et al (2011) DeltaNp63 regulates stem cell dynamics in the mammalian olfactory epithelium. J Neurosci 31(24):8748–8759PubMedPubMedCentralGoogle Scholar
  99. 99.
    Fletcher RB et al (2011) p63 regulates olfactory stem cell self-renewal and differentiation. Neuron 72(5):748–759PubMedPubMedCentralGoogle Scholar
  100. 100.
    Krolewski RC et al (2012) Ascl1 (Mash1) knockout perturbs differentiation of nonneuronal cells in olfactory epithelium. PLoS One 7(12):e51737PubMedPubMedCentralGoogle Scholar
  101. 101.
    Guillemot F et al (1993) Mammalian achaete-scute homolog 1 is required for the early development of olfactory and autonomic neurons. Cell 75(3):463–476PubMedGoogle Scholar
  102. 102.
    Deckner ML, Risling M, Frisen J (1997) Apoptotic death of olfactory sensory neurons in the adult rat. Exp Neurol 143(1):132–140PubMedGoogle Scholar
  103. 103.
    Wagner N et al (2005) A splice variant of the Wilms' tumour suppressor Wt1 is required for normal development of the olfactory system. Development 132(6):1327–1336PubMedGoogle Scholar
  104. 104.
    Nishimura M et al (1998) Structure, chromosomal locus, and promoter of mouse Hes2 gene, a homologue of Drosophila hairy and Enhancer of split. Genomics 49(1):69–75PubMedGoogle Scholar
  105. 105.
    Carson C, Murdoch B, Roskams AJ (2006) Notch 2 and Notch 1/3 segregate to neuronal and glial lineages of the developing olfactory epithelium. Dev Dyn 235(6):1678–1688PubMedGoogle Scholar
  106. 106.
    Ma Q et al (1997) Mash1 and neurogenin1 expression patterns define complementary domains of neuroepithelium in the developing CNS and are correlated with regions expressing notch ligands. J Neurosci 17(10):3644–3652PubMedGoogle Scholar
  107. 107.
    Packard A et al (2011) Progenitor cell capacity of NeuroD1-expressing globose basal cells in the mouse olfactory epithelium. J Comp Neurol 519(17):3580–3596PubMedPubMedCentralGoogle Scholar
  108. 108.
    Theriault FM et al (2005) Role for Runx1 in the proliferation and neuronal differentiation of selected progenitor cells in the mammalian nervous system. J Neurosci 25(8):2050–2061PubMedGoogle Scholar
  109. 109.
    Heron PM et al (2013) Molecular events in the cell types of the olfactory epithelium during adult neurogenesis. Mol Brain 6:49PubMedPubMedCentralGoogle Scholar
  110. 110.
    Berghard A et al (2012) Lhx2-dependent specification of olfactory sensory neurons is required for successful integration of olfactory, vomeronasal, and GnRH neurons. FASEB J 26(8):3464–3472PubMedGoogle Scholar
  111. 111.
    Hirota J, 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(23):8751–8755PubMedPubMedCentralGoogle Scholar
  112. 112.
    Kolterud A et al (2004) The Lim homeobox gene Lhx2 is required for olfactory sensory neuron identity. Development 131(21):5319–5326PubMedGoogle Scholar
  113. 113.
    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):679–688PubMedGoogle Scholar
  114. 114.
    Saha B et al (2007) Dual role for LIM-homeodomain gene Lhx2 in the formation of the lateral olfactory tract. J Neurosci 27(9):2290–2297PubMedPubMedCentralGoogle Scholar
  115. 115.
    Kudrycki K et al (1993) Olf-1-binding site: characterization of an olfactory neuron-specific promoter motif. Mol Cell Biol 13(5):3002–3014PubMedPubMedCentralGoogle Scholar
  116. 116.
    Wang MM et al (1993) Genes encoding components of the olfactory signal transduction cascade contain a DNA binding site that may direct neuronal expression. Mol Cell Biol 13(9):5805–5813PubMedPubMedCentralGoogle Scholar
  117. 117.
    Wang SS, Tsai RY, Reed RR (1997) The characterization of the Olf-1/EBF-like HLH transcription factor family: implications in olfactory gene regulation and neuronal development. J Neurosci 17(11):4149–4158PubMedGoogle Scholar
  118. 118.
    Wang SS, Betz AG, Reed RR (2002) Cloning of a novel Olf-1/EBF-like gene, O/E-4, by degenerate oligo-based direct selection. Mol Cell Neurosci 20(3):404–414PubMedGoogle Scholar
  119. 119.
    Lee AC, He J, Ma M (2011) Olfactory marker protein is critical for functional maturation of olfactory sensory neurons and development of mother preference. J Neurosci 31(8):2974–2982PubMedPubMedCentralGoogle Scholar
  120. 120.
    Wang SS et al (2004) Genetic disruptions of O/E2 and O/E3 genes reveal involvement in olfactory receptor neuron projection. Development 131(6):1377–1388PubMedGoogle Scholar
  121. 121.
    Behrens M et al (2000) NFI in the development of the olfactory neuroepithelium and the regulation of olfactory marker protein gene expression. Eur J Neurosci 12(4):1372–1384PubMedGoogle Scholar
  122. 122.
    Moon C et al (2002) Leukemia inhibitory factor inhibits neuronal terminal differentiation through STAT3 activation. Proc Natl Acad Sci U S A 99(13):9015–9020PubMedPubMedCentralGoogle Scholar
  123. 123.
    Baumeister H et al (1999) Identification of NFI-binding sites and cloning of NFI-cDNAs suggest a regulatory role for NFI transcription factors in olfactory neuron gene expression. Brain Res Mol Brain Res 72(1):65–79PubMedGoogle Scholar
  124. 124.
    Laub F et al (2001) Developmental expression of mouse Kruppel-like transcription factor KLF7 suggests a potential role in neurogenesis. Dev Biol 233(2):305–318PubMedGoogle Scholar
  125. 125.
    Laub F et al (2005) Transcription factor KLF7 is important for neuronal morphogenesis in selected regions of the nervous system. Mol Cell Biol 25(13):5699–5711PubMedPubMedCentralGoogle Scholar
  126. 126.
    Tsai RY, Reed RR (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(11):4159–4169PubMedGoogle Scholar
  127. 127.
    Cohen DR et al (2003) Expression of MeCP2 in olfactory receptor neurons is developmentally regulated and occurs before synaptogenesis. Mol Cell Neurosci 22(4):417–429PubMedGoogle Scholar
  128. 128.
    Matarazzo V et al (2004) The transcriptional repressor Mecp2 regulates terminal neuronal differentiation. Mol Cell Neurosci 27(1):44–58PubMedGoogle Scholar
  129. 129.
    Kajimura D et al (2007) Identification of genes regulated by transcription factor KLF7 in differentiating olfactory sensory neurons. Gene 388(1-2):34–42PubMedGoogle Scholar
  130. 130.
    Ishibashi M et al (1994) Persistent expression of helix-loop-helix factor HES-1 prevents mammalian neural differentiation in the central nervous system. EMBO J 13(8):1799–1805PubMedPubMedCentralGoogle Scholar
  131. 131.
    Kageyama R, Ohtsuka T (1999) The Notch-Hes pathway in mammalian neural development. Cell Res 9(3):179–188PubMedGoogle Scholar
  132. 132.
    Akazawa C et al (1992) Molecular characterization of a rat negative regulator with a basic helix-loop-helix structure predominantly expressed in the developing nervous system. J Biol Chem 267(30):21879–21885PubMedGoogle Scholar
  133. 133.
    Forni PE et al (2011) Neural crest and ectodermal cells intermix in the nasal placode to give rise to GnRH-1 neurons, sensory neurons, and olfactory ensheathing cells. J Neurosci 31(18):6915–6927PubMedPubMedCentralGoogle Scholar
  134. 134.
    Valverde F, Santacana M, Heredia M (1992) Formation of an olfactory glomerulus: morphological aspects of development and organization. Neuroscience 49(2):255–275PubMedGoogle Scholar
  135. 135.
    Miller AM, Treloar HB, Greer CA (2010) Composition of the migratory mass during development of the olfactory nerve. J Comp Neurol 518(24):4825–4841PubMedPubMedCentralGoogle Scholar
  136. 136.
    Hansen A, Finger TE (2008) Is TrpM5 a reliable marker for chemosensory cells? Multiple types of microvillous cells in the main olfactory epithelium of mice. BMC Neurosci 9:115PubMedPubMedCentralGoogle Scholar
  137. 137.
    Asan E, Drenckhahn D (2005) Immunocytochemical characterization of two types of microvillar cells in rodent olfactory epithelium. Histochem Cell Biol 123(2):157–168PubMedGoogle Scholar
  138. 138.
    Yamaguchi T et al (2014) Skn-1a/Pou2f3 is required for the generation of Trpm5-expressing microvillous cells in the mouse main olfactory epithelium. BMC Neurosci 15:13PubMedPubMedCentralGoogle Scholar
  139. 139.
    Murao N, Noguchi H, Nakashima K (2016) Epigenetic regulation of neural stem cell property from embryo to adult. Neuroepigenetics 5(Supplement C):1–10Google Scholar
  140. 140.
    Ho L, Crabtree GR (2010) Chromatin remodelling during development. Nature 463(7280):474–484PubMedPubMedCentralGoogle Scholar
  141. 141.
    Hu G et al (2011) Regulation of nucleosome landscape and transcription factor targeting at tissue-specific enhancers by BRG1. Genome Res 21(10):1650–1658PubMedPubMedCentralGoogle Scholar
  142. 142.
    Stokes DG, Perry RP (1995) DNA-binding and chromatin localization properties of CHD1. Mol Cell Biol 15(5):2745–2753PubMedPubMedCentralGoogle Scholar
  143. 143.
    Hall JA, Georgel PT (2007) CHD proteins: a diverse family with strong ties. Biochem Cell Biol 85(4):463–476PubMedGoogle Scholar
  144. 144.
    Vissers LE et al (2004) Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. Nat Genet 36(9):955–957PubMedGoogle Scholar
  145. 145.
    Lalani SR et al (2006) Spectrum of CHD7 mutations in 110 individuals with CHARGE syndrome and genotype-phenotype correlation. Am J Hum Genet 78(2):303–314PubMedGoogle Scholar
  146. 146.
    Aramaki M et al (2006) Phenotypic spectrum of CHARGE syndrome with CHD7 mutations. J Pediatr 148(3):410–414PubMedGoogle Scholar
  147. 147.
    Sanlaville D et al (2006) Phenotypic spectrum of CHARGE syndrome in fetuses with CHD7 truncating mutations correlates with expression during human development. J Med Genet 43(3):211–217PubMedGoogle Scholar
  148. 148.
    Jongmans MC et al (2006) CHARGE syndrome: the phenotypic spectrum of mutations in the CHD7 gene. J Med Genet 43(4):306–314PubMedGoogle Scholar
  149. 149.
    Bosman EA et al (2005) Multiple mutations in mouse Chd7 provide models for CHARGE syndrome. Hum Mol Genet 14(22):3463–3476PubMedGoogle Scholar
  150. 150.
    Adams ME et al (2007) Defects in vestibular sensory epithelia and innervation in mice with loss of Chd7 function: implications for human CHARGE syndrome. J Comp Neurol 504(5):519–532PubMedGoogle Scholar
  151. 151.
    Hurd EA et al (2007) Loss of Chd7 function in gene-trapped reporter mice is embryonic lethal and associated with severe defects in multiple developing tissues. Mamm Genome 18(2):94–104PubMedGoogle Scholar
  152. 152.
    Layman WS et al (2009) Defects in neural stem cell proliferation and olfaction in Chd7 deficient mice indicate a mechanism for hyposmia in human CHARGE syndrome. Hum Mol Genet 18(11):1909–1923PubMedPubMedCentralGoogle Scholar
  153. 153.
    Bergman JE et al (2010) Study of smell and reproductive organs in a mouse model for CHARGE syndrome. Eur J Hum Genet 18(2):171–177PubMedGoogle Scholar
  154. 154.
    Feng W et al (2017) Chd7 is indispensable for mammalian brain development through activation of a neuronal differentiation programme. Nat Commun 8:14758PubMedPubMedCentralGoogle Scholar
  155. 155.
    Schnetz MP et al (2009) Genomic distribution of CHD7 on chromatin tracks H3K4 methylation patterns. Genome Res 19(4):590–601PubMedPubMedCentralGoogle Scholar
  156. 156.
    Van Nostrand JL et al (2014) Inappropriate p53 activation during development induces features of CHARGE syndrome. Nature 514(7521):228–232PubMedPubMedCentralGoogle Scholar
  157. 157.
    Zentner GE et al (2010) Molecular and phenotypic aspects of CHD7 mutation in CHARGE syndrome. Am J Med Genet A 152A(3):674–686PubMedPubMedCentralGoogle Scholar
  158. 158.
    Neigeborn L, Carlson M (1984) Genes affecting the regulation of SUC2 gene expression by glucose repression in Saccharomyces cerevisiae. Genetics 108(4):845–858PubMedPubMedCentralGoogle Scholar
  159. 159.
    Wang W et al (1996) Purification and biochemical heterogeneity of the mammalian SWI-SNF complex. EMBO J 15(19):5370–5382PubMedPubMedCentralGoogle Scholar
  160. 160.
    Phelan ML et al (1999) Reconstitution of a core chromatin remodeling complex from SWI/SNF subunits. Mol Cell 3(2):247–253PubMedGoogle Scholar
  161. 161.
    Cairns BR (1998) Chromatin remodeling machines: similar motors, ulterior motives. Trends Biochem Sci 23(1):20–25PubMedGoogle Scholar
  162. 162.
    Whitehouse I et al (1999) Nucleosome mobilization catalysed by the yeast SWI/SNF complex. Nature 400(6746):784–787PubMedGoogle Scholar
  163. 163.
    Tang L, Nogales E, Ciferri C (2010) Structure and function of SWI/SNF chromatin remodeling complexes and mechanistic implications for transcription. Prog Biophys Mol Biol 102(2-3):122–128PubMedPubMedCentralGoogle Scholar
  164. 164.
    Gutierrez J et al (2007) Chromatin remodeling by SWI/SNF results in nucleosome mobilization to preferential positions in the rat osteocalcin gene promoter. J Biol Chem 282(13):9445–9457PubMedGoogle Scholar
  165. 165.
    Ho L et al (2009) An embryonic stem cell chromatin remodeling complex, esBAF, is essential for embryonic stem cell self-renewal and pluripotency. Proc Natl Acad Sci U S A 106(13):5181–5186PubMedPubMedCentralGoogle Scholar
  166. 166.
    Ho L et al (2009) An embryonic stem cell chromatin remodeling complex, esBAF, is an essential component of the core pluripotency transcriptional network. Proc Natl Acad Sci U S A 106(13):5187–91Google Scholar
  167. 167.
    Tuoc TC, Narayanan R, Stoykova A (2013) BAF chromatin remodeling complex: cortical size regulation and beyond. Cell Cycle 12(18):2953–2959PubMedPubMedCentralGoogle Scholar
  168. 168.
    Tuoc TC et al (2013) Chromatin regulation by BAF170 controls cerebral cortical size and thickness. Dev Cell 25(3):256–269PubMedGoogle Scholar
  169. 169.
    Hassenklöver T, Manzini I (2014) The olfactory system as a model to study axonal growth patterns and morphology in vivo. J Vis Exp: JoVE 92:52143Google Scholar
  170. 170.
    Tuoc T et al (2017) Ablation of BAF170 in developing and postnatal dentate gyrus affects neural stem cell proliferation, differentiation, and learning. Mol Neurobiol 54(6):4618–4635PubMedGoogle Scholar
  171. 171.
    Lessard J et al (2007) An essential switch in subunit composition of a chromatin remodeling complex during neural development. Neuron 55(2):201–215PubMedPubMedCentralGoogle Scholar
  172. 172.
    Wu JI et al (2007) Regulation of dendritic development by neuron-specific chromatin remodeling complexes. Neuron 56(1):94–108PubMedGoogle Scholar
  173. 173.
    Narayanan R et al (2015) Loss of BAF (mSWI/SNF) complexes causes global transcriptional and chromatin state changes in forebrain development. Cell Rep 13(9):1842–1854PubMedGoogle Scholar
  174. 174.
    Harikrishnan KN et al (2005) Brahma links the SWI/SNF chromatin-remodeling complex with MeCP2-dependent transcriptional silencing. Nat Genet 37(3):254–264PubMedGoogle Scholar
  175. 175.
    Degano AL et al (2014) MeCP2 is required for activity-dependent refinement of olfactory circuits. Mol Cell Neurosci 59:63–75PubMedPubMedCentralGoogle Scholar
  176. 176.
    Macdonald JL et al (2010) MBD2 and MeCP2 regulate distinct transitions in the stage-specific differentiation of olfactory receptor neurons. Mol Cell Neurosci 44(1):55–67PubMedGoogle Scholar
  177. 177.
    Ho L et al (2011) esBAF facilitates pluripotency by conditioning the genome for LIF/STAT3 signalling and by regulating polycomb function. Nat Cell Biol 13(8):903–913PubMedPubMedCentralGoogle Scholar
  178. 178.
    Boyer LA et al (2005) Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122(6):947–956PubMedPubMedCentralGoogle Scholar
  179. 179.
    Kadoch C et al (2017) Dynamics of BAF-Polycomb complex opposition on heterochromatin in normal and oncogenic states. Nat Genet 49(2):213–222PubMedGoogle Scholar
  180. 180.
    Hirabayashi Y, Gotoh Y (2010) Epigenetic control of neural precursor cell fate during development. Nat Rev Neurosci 11(6):377–388PubMedGoogle Scholar
  181. 181.
    Bernstein BE, Meissner A, Lander ES (2007) The mammalian epigenome. Cell 128(4):669–681PubMedGoogle Scholar
  182. 182.
    Kouzarides T (2007) Chromatin modifications and their function. Cell 128(4):693–705PubMedGoogle Scholar
  183. 183.
    Margueron R, Reinberg D (2010) Chromatin structure and the inheritance of epigenetic information. Nat Rev Genet 11(4):285–296PubMedPubMedCentralGoogle Scholar
  184. 184.
    Ruthenburg AJ et al (2007) Multivalent engagement of chromatin modifications by linked binding modules. Nat Rev Mol Cell Biol 8(12):983–994PubMedPubMedCentralGoogle Scholar
  185. 185.
    Tessarz P, Kouzarides T (2014) Histone core modifications regulating nucleosome structure and dynamics. Nat Rev Mol Cell Biol 15(11):703–708PubMedGoogle Scholar
  186. 186.
    Kornberg RD (1974) Chromatin structure: a repeating unit of histones and DNA. Science 184(4139):868–871PubMedGoogle Scholar
  187. 187.
    Wang Y et al (2004) Linking covalent histone modifications to epigenetics: the rigidity and plasticity of the marks. Cold Spring Harb Symp Quant Biol 69:161–169PubMedGoogle Scholar
  188. 188.
    Shi Y et al (2004) Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119(7):941–953PubMedGoogle Scholar
  189. 189.
    Metzger E et al (2005) LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature 437(7057):436–439PubMedGoogle Scholar
  190. 190.
    Shi Y et al (2004) Expression and function of orphan nuclear receptor TLX in adult neural stem cells. Nature 427(6969):78–83PubMedGoogle Scholar
  191. 191.
    Garcia-Bassets I et al (2007) Histone methylation-dependent mechanisms impose ligand dependency for gene activation by nuclear receptors. Cell 128(3):505–518PubMedPubMedCentralGoogle Scholar
  192. 192.
    Laurent B et al (2015) A specific LSD1/KDM1A isoform regulates neuronal differentiation through H3K9 demethylation. Mol Cell 57(6):957–970PubMedPubMedCentralGoogle Scholar
  193. 193.
    Sun G et al (2010) Histone demethylase LSD1 regulates neural stem cell proliferation. Mol Cell Biol 30(8):1997–2005PubMedPubMedCentralGoogle Scholar
  194. 194.
    Lyons DB et al (2013) An epigenetic trap stabilizes singular olfactory receptor expression. Cell 154(2):325–336PubMedPubMedCentralGoogle Scholar
  195. 195.
    Coleman JH, Lin B, Schwob JE (2017) Dissecting LSD1-dependent neuronal maturation in the olfactory epithelium. J Comp Neurol 525(16):3391–3413PubMedGoogle Scholar
  196. 196.
    Krolewski RC, Packard A, Schwob JE (2013) Global expression profiling of globose basal cells and neurogenic progression within the olfactory epithelium. J Comp Neurol 521(4):833–859PubMedGoogle Scholar
  197. 197.
    Kilinc S et al (2016) Lysine-specific demethylase-1 (LSD1) is compartmentalized at nuclear chromocenters in early post-mitotic cells of the olfactory sensory neuronal lineage. Mol Cell Neurosci 74:58–70PubMedPubMedCentralGoogle Scholar
  198. 198.
    Magklara A et al (2011) An epigenetic signature for monoallelic olfactory receptor expression. Cell 145(4):555–570PubMedPubMedCentralGoogle Scholar
  199. 199.
    Lyons DB et al (2014) Heterochromatin-mediated gene silencing facilitates the diversification of olfactory neurons. Cell Rep 9(3):884–892PubMedPubMedCentralGoogle Scholar
  200. 200.
    Okano M et al (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99(3):247–257PubMedGoogle Scholar
  201. 201.
    Li E, Bestor TH, Jaenisch R (1992) Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69(6):915–926PubMedGoogle Scholar
  202. 202.
    Nguyen S et al (2007) Ablation of de novo DNA methyltransferase Dnmt3a in the nervous system leads to neuromuscular defects and shortened lifespan. Dev Dyn 236(6):1663–1676PubMedGoogle Scholar
  203. 203.
    Chahrour M, Zoghbi HY (2007) The story of Rett syndrome: from clinic to neurobiology. Neuron 56(3):422–437PubMedGoogle Scholar
  204. 204.
    Cheng X et al (1993) Crystal structure of the HhaI DNA methyltransferase complexed with S-adenosyl-L-methionine. Cell 74(2):299–307PubMedGoogle Scholar
  205. 205.
    Klose RJ, Bird AP (2006) Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci 31(2):89–97PubMedGoogle Scholar
  206. 206.
    Wu H et al (2010) Dnmt3a-dependent nonpromoter DNA methylation facilitates transcription of neurogenic genes. Science 329(5990):444–448PubMedPubMedCentralGoogle Scholar
  207. 207.
    Robertson KD (2005) DNA methylation and human disease. Nat Rev Genet 6(8):597–610PubMedGoogle Scholar
  208. 208.
    Leonhardt H et al (1992) A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell 71(5):865–873PubMedGoogle Scholar
  209. 209.
    Feng J, Fouse S, Fan G (2007) Epigenetic regulation of neural gene expression and neuronal function. Pediatr Res 61(5 Pt 2):58R–63RPubMedGoogle Scholar
  210. 210.
    Hutnick LK et al (2009) DNA hypomethylation restricted to the murine forebrain induces cortical degeneration and impairs postnatal neuronal maturation. Hum Mol Genet 18(15):2875–2888PubMedPubMedCentralGoogle Scholar
  211. 211.
    Podobinska M et al (2017) Epigenetic modulation of stem cells in neurodevelopment: the role of methylation and acetylation. Front Cell Neurosci 11:23PubMedPubMedCentralGoogle Scholar
  212. 212.
    MacDonald JL, Gin CS, Roskams AJ (2005) Stage-specific induction of DNA methyltransferases in olfactory receptor neuron development. Dev Biol 288(2):461–473PubMedGoogle Scholar
  213. 213.
    Franco I et al (2017) Pharmacological inhibition of DNA methyltransferase 1 promotes neuronal differentiation from rodent and human nasal olfactory stem/progenitor cell cultures. Int J Dev Neurosci 58:65–73PubMedGoogle Scholar
  214. 214.
    Colquitt BM et al (2014) Dnmt3a regulates global gene expression in olfactory sensory neurons and enables odorant-induced transcription. Neuron 83(4):823–838PubMedPubMedCentralGoogle Scholar
  215. 215.
    Ambros V (2004) The functions of animal microRNAs. Nature 431(7006):350–355PubMedGoogle Scholar
  216. 216.
    Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297PubMedGoogle Scholar
  217. 217.
    Du T, Zamore PD (2005) microPrimer: the biogenesis and function of microRNA. Development 132(21):4645–4652PubMedGoogle Scholar
  218. 218.
    Agostini M et al (2011) microRNA-34a regulates neurite outgrowth, spinal morphology, and function. Proc Natl Acad Sci U S A 108(52):21099–21104PubMedPubMedCentralGoogle Scholar
  219. 219.
    Aranha MM et al (2011) miR-34a regulates mouse neural stem cell differentiation. PLoS One 6(8):e21396PubMedPubMedCentralGoogle Scholar
  220. 220.
    Brett JO et al (2011) The microRNA cluster miR-106b~25 regulates adult neural stem/progenitor cell proliferation and neuronal differentiation. Aging (Albany NY) 3(2):108–124Google Scholar
  221. 221.
    Gaughwin P et al (2011) Stage-specific modulation of cortical neuronal development by Mmu-miR-134. Cereb Cortex 21(8):1857–1869PubMedGoogle Scholar
  222. 222.
    Luikart BW et al (2011) miR-132 mediates the integration of newborn neurons into the adult dentate gyrus. PLoS One 6(5):e19077PubMedPubMedCentralGoogle Scholar
  223. 223.
    Olde Loohuis NF et al (2012) MicroRNA networks direct neuronal development and plasticity. Cell Mol Life Sci 69(1):89–102PubMedGoogle Scholar
  224. 224.
    Shi Y et al (2010) MicroRNA regulation of neural stem cells and neurogenesis. J Neurosci 30(45):14931–14936PubMedPubMedCentralGoogle Scholar
  225. 225.
    Li X, Carthew RW (2005) A microRNA mediates EGF receptor signaling and promotes photoreceptor differentiation in the Drosophila eye. Cell 123(7):1267–1277PubMedGoogle Scholar
  226. 226.
    Chang S et al (2004) MicroRNAs act sequentially and asymmetrically to control chemosensory laterality in the nematode. Nature 430(7001):785–789PubMedGoogle Scholar
  227. 227.
    Johnston RJ, Hobert O (2003) A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans. Nature 426(6968):845–849PubMedGoogle Scholar
  228. 228.
    Xu S et al (2007) MicroRNA (miRNA) transcriptome of mouse retina and identification of a sensory organ-specific miRNA cluster. J Biol Chem 282(34):25053–25066PubMedGoogle Scholar
  229. 229.
    Zhao Y et al (2013) Early development of the gonadotropin-releasing hormone neuronal network in transgenic zebrafish. Front Endocrinol (Lausanne) 4:107Google Scholar
  230. 230.
    Garaffo G et al (2015) The Dlx5 and Foxg1 transcription factors, linked via miRNA-9 and -200, are required for the development of the olfactory and GnRH system. Mol Cell Neurosci 68:103–119PubMedPubMedCentralGoogle Scholar
  231. 231.
    Harfe BD et al (2005) The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb. Proc Natl Acad Sci U S A 102(31):10898–10903PubMedPubMedCentralGoogle Scholar
  232. 232.
    Aranha MM et al (2010) Apoptosis-associated microRNAs are modulated in mouse, rat and human neural differentiation. BMC Genomics 11:514PubMedPubMedCentralGoogle Scholar
  233. 233.
    Levi G et al (2003) The Dlx5 homeodomain gene is essential for olfactory development and connectivity in the mouse. Mol Cell Neurosci 22(4):530–543PubMedGoogle Scholar
  234. 234.
    Fan J et al (2017) Maturation arrest in early postnatal sensory receptors by deletion of the miR-183/96/182 cluster in mouse. Proc Natl Acad Sci U S A 114(21):E4271–E4280PubMedPubMedCentralGoogle Scholar
  235. 235.
    Lavoie J, Sawa A, Ishizuka K (2017) Application of olfactory tissue and its neural progenitors to schizophrenia and psychiatric research. Curr Opin Psychiatry 30(3):176–183PubMedPubMedCentralGoogle Scholar
  236. 236.
    Packard AI, Lin B, Schwob JE (2016) Sox2 and Pax6 play counteracting roles in regulating neurogenesis within the murine olfactory epithelium. PLoS ONE 11(5):e0155167PubMedPubMedCentralGoogle Scholar
  237. 237.
    Rosenbaum JN, Duggan A, Garcia-Anoveros J (2011) Insm1 promotes the transition of olfactory progenitors from apical and proliferative to basal, terminally dividing and neuronogenic. Neural Dev 6:6PubMedPubMedCentralGoogle Scholar
  238. 238.
    Sammeta N, Hardin DL, McClintock TS (2010) Uncx regulates proliferation of neural progenitor cells and neuronal survival in the olfactory epithelium. Mol Cell Neurosci 45(4):398–407PubMedPubMedCentralGoogle Scholar
  239. 239.
    Shaker T et al (2012) Neurog1 and Neurog2 coordinately regulate development of the olfactory system. Neural Dev 7:28PubMedPubMedCentralGoogle Scholar
  240. 240.
    Kawauchi S et al (2009) The role of foxg1 in the development of neural stem cells of the olfactory epithelium. Ann N Y Acad Sci 1170:21–27PubMedPubMedCentralGoogle Scholar
  241. 241.
    Kawauchi S et al (2009) Foxg1 promotes olfactory neurogenesis by antagonizing Gdf11. Development 136(9):1453–1464PubMedPubMedCentralGoogle Scholar
  242. 242.
    Murthy M et al (2014) Transcription factor Runx1 inhibits proliferation and promotes developmental maturation in a selected population of inner olfactory nerve layer olfactory ensheathing cells. Gene 540(2):191–200PubMedGoogle Scholar
  243. 243.
    Wittmann W, Iulianella A, Gunhaga L (2014) Cux2 acts as a critical regulator for neurogenesis in the olfactory epithelium of vertebrates. Dev Biol 388(1):35–47PubMedGoogle Scholar
  244. 244.
    Wittmann W, Schimmang T, Gunhaga L (2014) Progressive effects of N-myc deficiency on proliferation, neurogenesis, and morphogenesis in the olfactory epithelium. Dev Neurobiol 74(6):643–656PubMedGoogle Scholar
  245. 245.
    Ikeda K et al (2010) Six1 is indispensable for production of functional progenitor cells during olfactory epithelial development. Int J Dev Biol 54(10):1453–1464PubMedGoogle Scholar
  246. 246.
    Yoshihara S et al (2005) Arx homeobox gene is essential for development of mouse olfactory system. Development 132(4):751–762PubMedGoogle Scholar
  247. 247.
    Lemons K et al (2017) Lack of TRPM5-expressing microvillous cells in mouse main olfactory epithelium leads to impaired odor-evoked responses and olfactory-guided behavior in a challenging chemical environment. eNeuro 4(3).PubMedPubMedCentralGoogle Scholar
  248. 248.
    Enomoto T et al (2011) Bcl11b/Ctip2 controls the differentiation of vomeronasal sensory neurons in mice. J Neurosci off J Soc Neurosci 31(28):10159–10173Google Scholar
  249. 249.
    Lee W et al (2014) MeCP2 regulates activity-dependent transcriptional responses in olfactory sensory neurons. Hum Mol Genet 23(23):6366–6374PubMedPubMedCentralGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of Neuroanatomy, University Medical CenterGeorg-August-University GoettingenGoettingenGermany
  2. 2.Zoology Department, Faculty of ScienceAlexandria UniversityAlexandriaEgypt
  3. 3.DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB)GoettingenGermany

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