Advertisement

Neurochemical Research

, Volume 36, Issue 7, pp 1261–1269 | Cite as

Expression and Function of Sox21 During Mouse Cochlea Development

  • Makoto Hosoya
  • Masato Fujioka
  • Satoru Matsuda
  • Hiroyuki Ohba
  • Shinsuke Shibata
  • Fumiko Nakagawa
  • Takahisa Watabe
  • Ken-ichiro Wakabayashi
  • Yumiko Saga
  • Kaoru Ogawa
  • Hirotaka James Okano
  • Hideyuki Okano
Original Paper

Abstract

The development of the inner ear is an orchestrated process of morphogenesis with spatiotemporally controlled generations of individual cell types. Recent studies have revealed that the Sox gene family, a family of evolutionarily conserved HMG-type transcriptional factors, is differentially expressed in each cell type of the mammalian inner ear and plays critical roles in cell-fate determination during development. In this study, we examined the expression pattern of Sox21 in the developing and adult murine cochlea. Sox21 was expressed throughout the sensory epithelium in the early otocyst stage but became restricted to supporting cells during adulthood. Interestingly, the expression in adults was restricted to the inner phalangeal, inner border, and Deiters’ cells: all of these cells are in direct contact with hair cells. Evaluations of the auditory brainstem-response revealed that Sox21−/− mice suffered mild hearing impairments, with an increase in hair cells that miss their appropriate planar cell polarity. Taken together with the previously reported critical roles of SoxB1 families in the morphogenesis of inner ear sensory and neuronal cells, our results suggest that Sox21, a counteracting partner of the SoxB1 family, controls fine-tuned cell fate decisions. Also, the characteristic expression pattern may be useful for labelling a particular subset of supporting cells.

Keywords

Inner ear Cochlea Development Sox21 Hair cell Supporting cell 

Notes

Acknowledgments

We thank Ms. Ayano Mitsui and Dr. T. Nagai for their technical assistance and Dr. Junko Murata (Osaka University) for technical advices. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), the Japan Science and Technology Corporation (JST), and the Funding Program for World-leading Innovative R&D on Science and Technology to H.O., and by a Grant-in-Aid for Scientific Research B (20390444) to K.O., and by a Research on Measures for Intractable Diseases from the Ministry of Health, Labor and Welfare of Japan to M.F., and by a Keio University grant-in-aid for encouragement of young medical scientists to M.F., and by a Keio Gijuku Academic Development Funds to M.F. and by a Grant-in-Aid for Young Scientists B (22791628) to M.F. from MEXT. and by a grant-in-aid from the Global COE Program of MEXT, Japan to Keio University.

Supplementary material

11064_2011_416_MOESM1_ESM.tif (1 mb)
Double labeling of EGFP and Sox21 protein. All of the nuclei of EGFP-positive cells were labeled with anti-Sox21 antibody (red), indicating that the EGFP-expression in Sox21/EGFP mouse reflects endogenous protein expression of Sox21. (Scale Bar: 50 μm in A) (TIFF 1025 kb)
11064_2011_416_MOESM2_ESM.tif (140 kb)
ABR threshold of all mice tested. Hearing function of both wild type and knock out was tested (N = 3 and 4, respectably). At both frequencies, threshold was elevated in knock out in comparison to wildtype (TIFF 139 kb)

References

  1. 1.
    Dabdoub A, Puligilla C, Jones JM et al (2008) Sox2 signaling in prosensory domain specification and subsequent hair cell differentiation in the developing cochlea. Proc Natl Acad Sci USA 105:18396–18401PubMedCrossRefGoogle Scholar
  2. 2.
    Puligilla C, Dabdoub A, Brenowitz SD et al (2010) Sox2 induces neuronal formation in the developing mammalian cochlea. J Neurosci 30:714–722PubMedCrossRefGoogle Scholar
  3. 3.
    Uchikawa M, Kamachi Y, Kondoh H (1999) Two distinct subgroups of Group B Sox genes for transcriptional activators and repressors: their expression during embryonic organogenesis of the chicken. Mech Dev 84:103–120PubMedCrossRefGoogle Scholar
  4. 4.
    Bowles J, Schepers G, Koopman P (2000) Phylogeny of the SOX family of developmental transcription factors based on sequence and structural indicators. Dev Biol 227:239–255PubMedCrossRefGoogle Scholar
  5. 5.
    Bani-Yaghoub M, Tremblay RG, Lei JX et al (2006) Role of Sox2 in the development of the mouse neocortex. Dev Biol 295:52–66PubMedCrossRefGoogle Scholar
  6. 6.
    Bylund M, Andersson E, Novitch BG et al (2003) Vertebrate neurogenesis is counteracted by Sox1-3 activity. Nat Neurosci 6:1162–1168PubMedCrossRefGoogle Scholar
  7. 7.
    Favaro R, Valotta M, Ferri AL et al (2009) Hippocampal development and neural stem cell maintenance require Sox2-dependent regulation of Shh. Nat Neurosci 12:1248–1256PubMedCrossRefGoogle Scholar
  8. 8.
    Ferri AL, Cavallaro M, Braida D et al (2004) Sox2 deficiency causes neurodegeneration and impaired neurogenesis in the adult mouse brain. Development 131:3805–3819PubMedCrossRefGoogle Scholar
  9. 9.
    Kan L, Israsena N, Zhang Z et al (2004) Sox1 acts through multiple independent pathways to promote neurogenesis. Dev Biol 269:580–594PubMedCrossRefGoogle Scholar
  10. 10.
    Wang TW, Stromberg GP, Whitney JT et al (2006) Sox3 expression identifies neural progenitors in persistent neonatal and adult mouse forebrain germinative zones. J Comp Neurol 497:88–100PubMedCrossRefGoogle Scholar
  11. 11.
    Sandberg M, Kallstrom M, Muhr J (2005) Sox21 promotes the progression of vertebrate neurogenesis. Nat Neurosci 8:995–1001PubMedCrossRefGoogle Scholar
  12. 12.
    Kiso M, Tanaka S, Saba R et al (2009) The disruption of Sox21-mediated hair shaft cuticle differentiation causes cyclic alopecia in mice. Proc Natl Acad Sci USA 106:9292–9297PubMedCrossRefGoogle Scholar
  13. 13.
    Masuda M, Nagashima R, Kanzaki S et al (2006) Nuclear factor-kappa B nuclear translocation in the cochlea of mice following acoustic overstimulation. Brain Res 1068:237–247PubMedCrossRefGoogle Scholar
  14. 14.
    Mizutari K, Fujioka M, Nakagawa S et al (2010) Balance dysfunction resulting from acute inner ear energy failure is caused primarily by vestibular hair cell damage. J Neurosci Res 88:1262–1272PubMedGoogle Scholar
  15. 15.
    Fujioka M, Kanzaki S, Okano HJ et al (2006) Proinflammatory cytokines expression in noise-induced damaged cochlea. J Neurosci Res 83:575–583PubMedCrossRefGoogle Scholar
  16. 16.
    Lawoko-Kerali G, Rivolta MN, Lawlor P et al (2004) GATA3 and NeuroD distinguish auditory and vestibular neurons during development of the mammalian inner ear. Mech Dev 121:287–299PubMedCrossRefGoogle Scholar
  17. 17.
    Kiernan AE, Pelling AL, Leung KK et al (2005) Sox2 is required for sensory organ development in the mammalian inner ear. Nature 434:1031–1035PubMedCrossRefGoogle Scholar
  18. 18.
    Hume CR, Bratt DL, Oesterle EC (2007) Expression of LHX3 and SOX2 during mouse inner ear development. Gene Expr Patterns 7:798–807PubMedCrossRefGoogle Scholar
  19. 19.
    Mak AC, Szeto IY, Fritzsch B et al (2009) Differential and overlapping expression pattern of SOX2 and SOX9 in inner ear development. Gene Expr Patterns 9:444–453PubMedCrossRefGoogle Scholar
  20. 20.
    Ohba H, Chiyoda T, Endo E et al (2004) Sox21 is a repressor of neuronal differentiation and is antagonized by YB-1. Neurosci Lett 358:157–160PubMedCrossRefGoogle Scholar
  21. 21.
    Zine A, Aubert A, Qiu J et al (2001) Hes1 and Hes5 activities are required for the normal development of the hair cells in the mammalian inner ear. J Neurosci 21:4712–4720PubMedGoogle Scholar
  22. 22.
    Sage C, Huang M, Vollrath MA et al (2006) Essential role of retinoblastoma protein in mammalian hair cell development and hearing. Proc Natl Acad Sci USA 103:7345–7350PubMedCrossRefGoogle Scholar
  23. 23.
    Rio C, Dikkes P, Liberman MC et al (2002) Glial fibrillary acidic protein expression and promoter activity in the inner ear of developing and adult mice. J Comp Neurol 442:156–162PubMedCrossRefGoogle Scholar
  24. 24.
    Coppens AG, Kiss R, Heizmann CW et al (2001) Immunolocalization of the calcium binding S100A1, S100A5 and S100A6 proteins in the dog cochlea during postnatal development. Brain Res Dev Brain Res 126:191–199PubMedCrossRefGoogle Scholar
  25. 25.
    Bermingham-McDonogh O, Oesterle EC, Stone JS et al (2006) Expression of Prox1 during mouse cochlear development. J Comp Neurol 496:172–186PubMedCrossRefGoogle Scholar
  26. 26.
    Bianchi LM, Liu H, Krug EL et al (1999) Selective and transient expression of a native chondroitin sulfate epitope in Deiters’ cells, pillar cells, and the developing tectorial membrane. Anat Rec 256:64–71PubMedCrossRefGoogle Scholar
  27. 27.
    Sato T, Doi K, Taniguchi M et al (2006) Progressive hearing loss in mice carrying a mutation in the p75 gene. Brain Res 1091:224–234PubMedCrossRefGoogle Scholar
  28. 28.
    Murata J, Tokunaga A, Okano H et al (2006) Mapping of notch activation during cochlear development in mice: implications for determination of prosensory domain and cell fate diversification. J Comp Neurol 497:502–518PubMedCrossRefGoogle Scholar
  29. 29.
    Jin ZH, Kikuchi T, Tanaka K et al (2003) Expression of glutamate transporter GLAST in the developing mouse cochlea. Tohoku J Exp Med 200:137–144PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Makoto Hosoya
    • 1
  • Masato Fujioka
    • 1
    • 2
  • Satoru Matsuda
    • 1
  • Hiroyuki Ohba
    • 1
  • Shinsuke Shibata
    • 1
  • Fumiko Nakagawa
    • 1
  • Takahisa Watabe
    • 2
  • Ken-ichiro Wakabayashi
    • 2
  • Yumiko Saga
    • 3
  • Kaoru Ogawa
    • 2
  • Hirotaka James Okano
    • 1
  • Hideyuki Okano
    • 1
  1. 1.Department of Physiology, School of MedicineKeio UniversityTokyoJapan
  2. 2.Department of Otolaryngology, Head and Neck Surgery, School of MedicineKeio UniversityTokyoJapan
  3. 3.Division of Mammalian Development and Mammalian GeneticsNational Institute of GeneticsMishimaJapan

Personalised recommendations