Skip to main content
SpringerLink
Log in

Vestibular Development

  • Chapter
  • First Online:
Regenerative Medicine for the Inner Ear

  • 1002 Accesses

Abstract

The vestibule consists of the semicircular canals and otolithic apparatus, which perceives the sense of equilibrium. The vestibule derives from the otocyst, which is mimicked by signaling information from its surrounding tissues to acquire its special disposition along three axes. The three semicircular canals and their cristae are derived from two evaginations of the otocyst. As the canal pouches increase in size, the opposing epithelia in the central portion of the structures merge toward each other to form a fusion plate. The fusion plates are eventually resorbed and the remaining edge of the pouch develops into a semicircular canal. The otolithic apparatus, which has characteristically uniform sensory epithelia, is also derived from the otocyst.

In this section, an overview of vestibular development and the molecular mechanism is described. Most of the data are from experiments using mouse, which has the most comprehensive model system for the developing mammalian cochlea.

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

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Wu DK, Kelley MW. Molecular mechanisms of inner ear development. Cold Spring Harb Perspect Biol. 2012;4(8):a008409. doi:10.1101/cshperspect.a008409.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Deansa MR. A balance of form and function: planar polarity and development of the vestibular maculae. Semin Cell Dev Biol. 2013;24(5):490–8. doi:10.1016/j.semcdb.2013.03.001.

    Article  Google Scholar 

  3. Riccomagno MM, Takada S, Epstein DJ. Wnt-dependent regulation of inner ear morphogenesis is balanced by the opposing and supporting roles of Shh. Genes Dev. 2005;19(13):1612–23.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Acampora D, Merlo GR, Paleari L, Zerega B, Postiglione MP, Mantero S, Bober E, Barbieri O, Simeone A, Levi G. Craniofacial, vestibular and bone defects in mice lacking the Distal-less-related gene Dlx5. Development. 1999;126(17):3795–809.

    CAS  PubMed  Google Scholar 

  5. Depew MJ, Liu JK, Long JE, Presley R, Meneses JJ, Pedersen RA, Rubenstein JL. Dlx5 regulates regional development of the branchial arches and sensory capsules. Development. 1999;126:3831–46.

    CAS  PubMed  Google Scholar 

  6. Merlo GR, Paleari L, Mantero S, Zerega B, Adamska M, Rinkwitz S, Bober E, Levi G. The Dlx5 homeobox gene is essential for vestibular morphogenesis in the mouse embryo through a BMP4-mediated pathway. Dev Biol. 2002;248(1):157–69.

    Article  CAS  PubMed  Google Scholar 

  7. Hadrys T, Braun T, Rinkwitz-Brandt S, Arnold HH, Bober E. Nkx5-1 controls semicircular canal formation in the mouse inner ear. Development. 1998;125(1):33–9.

    CAS  PubMed  Google Scholar 

  8. Wang W, Van De Water T, Lufkin T. Inner ear and maternal reproductive defects in mice lacking the Hmx3 homeobox gene. Development. 1998;125(4):621–34.

    CAS  PubMed  Google Scholar 

  9. Urness LD, Paxton CN, Wang X, Schoenwolf GC, Mansour SL. FGF signaling regulates otic placode induction and refinement by controlling both ectodermal target genes and hindbrain Wnt8a. Dev Biol. 2010;340(2):595–604. doi:10.1016/j.ydbio.2010.02.016.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Brown AS, Epstein DJ. Otic ablation of smoothened reveals direct and indirect requirement for Hedgehog signaling in inner ear development. Development. 2011;138(18):3967–76. doi:10.1242/dev.066126.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Liang JK, Bok J, Wu DK. Distinct contributions from the hindbrain and mesenchyme to inner ear morphogenesis. Dev Biol. 2010;337(2):324–34. doi:10.1016/j.ydbio.2009.11.001.

    Article  CAS  PubMed  Google Scholar 

  12. ten Berge D, Brouwer A, Korving J, Martin JF, Meijlink F. Prx1 and Prx2 in skeletogenesis: roles in the craniofacial region, inner ear and limbs. Development. 1998;125(19):3831–42.

    PubMed  Google Scholar 

  13. Phippard D, Lu L, Lee D, Saunders JC, Crenshaw III EB. Targeted mutagenesis of the POU-domain gene Brn4/Pou3f4 causes developmental defects in the inner ear. J Neurosci. 1999;19(14):5980–9.

    CAS  PubMed  Google Scholar 

  14. Sobol SE, Teng X, Crenshaw 3rd EB. Abnormal mesenchymal differentiation in the superior semicircular canal of Brn4/Pou3f4 knockout mice. Arch Otolaryngol Head Neck Surg. 2005;131(1):41–5.

    Article  PubMed  Google Scholar 

  15. Brigande JV, Iten LE, Fekete DM. A fate map of chick otic cup closure reveals lineage boundaries in the dorsal otocyst. Dev Biol. 2000;227(2):256–70.

    Article  CAS  PubMed  Google Scholar 

  16. Martin P, Swanson GJ. Descriptive and experimental analysis of the epithelial remodellings that control semicircular canal formation in the developing mouse inner ear. Dev Biol. 1993;159(2):549–58.

    Article  CAS  PubMed  Google Scholar 

  17. Chang W, Brigande JV, Fekete DM, Wu DK. The development of semicircular canals in the inner ear: role of FGFs in sensory cristae. Development. 2004;131(17):4201–11.

    Article  CAS  PubMed  Google Scholar 

  18. Cantos R, Cole LK, Acampora D, Simeone A, Wu DK. Patterning of the mammalian cochlea. Proc Natl Acad Sci U S A. 2000;97(22):11707–13.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Chang W, Nunes FD, De Jesus-Escobar JM, Harland R, Wu DK. Ectopic noggin blocks sensory and nonsensory organ morphogenesis in the chicken inner ear. Dev Biol. 1999;216(1):369–81.

    Article  CAS  PubMed  Google Scholar 

  20. Chang W, Lin Z, Kulessa H, Hebert J, Hogan BL, Wu DK. Bmp4 is essential for the formation of the vestibular apparatus that detects angular head movements. PLoS Genet. 2008;4(4):e1000050. doi:10.1371/journal.pgen.1000050.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Gerlach LM, Hutson MR, Germiller JA, Nguyen-Luu D, Victor JC, Barald KF. Addition of the BMP4 antagonist, noggin, disrupts avian inner ear development. Development. 2000;127(1):45–54.

    CAS  PubMed  Google Scholar 

  22. Ohta S, Mansour SL, Schoenwolf GC. BMP/SMAD signaling regulates the cell behaviors that drive the initial dorsal-specific regional morphogenesis of the otocyst. Dev Biol. 2010;347(2):369–81. doi:10.1016/j.ydbio.2010.09.002.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Morsli H, Choo D, Ryan A, Johnson R, Wu DK. Development of the mouse inner ear and origin of its sensory organs. J Neurosci. 1998;18(9):3327–35.

    CAS  PubMed  Google Scholar 

  24. Fritzsch B, Signore M, Simeone A. Otx1 null mutant mice show partial segregation of sensory epithelia comparable to lamprey ears. Dev Genes Evol. 2001;211(8–9):388–96.

    Article  CAS  PubMed  Google Scholar 

  25. Wang W, Chan EK, Baron S, Van de Water T, Lufkin T. Hmx2 homeobox gene control of murine vestibular morphogenesis. Development. 2001;128(24):5017–29.

    CAS  PubMed  Google Scholar 

  26. Wang W, Grimmer JF, Van De Water TR, Lufkin T. Hmx2 and Hmx3 homeobox genes direct development of the murine inner ear and hypothalamus and can be functionally replaced by Drosophila Hmx. Dev Cell. 2004;7(3):439–53.

    Article  CAS  PubMed  Google Scholar 

  27. Lin Z, Cantos R, Patente M, Wu DK. Gbx2 is required for the morphogenesis of the mouse inner ear: a downstream candidate of hindbrain signaling. Development. 2005;132(10):2309–18.

    Article  CAS  PubMed  Google Scholar 

  28. Hammond KL, Whitfield TT. The developing lamprey ear closely resembles the zebrafish otic vesicle: otx1 expression can account for all major patterning differences. Development. 2006;133(7):1347–57.

    Article  CAS  PubMed  Google Scholar 

  29. Dutton K, Abbas L, Spencer J, Brannon C, Mowbray C, Nikaido M, Kelsh RN, Whitfield TT. A zebrafish model for Waardenburg syndrome type IV reveals diverse roles for Sox10 in the otic vesicle. Dis Model Mech. 2009;2(1–2):68–83. doi:10.1242/dmm.001164.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Deng M, Pan L, Xie X, Gan L. Requirement for Lmo4 in the vestibular morphogenesis of mouse inner ear. Dev Biol. 2010;338(1):38–49. doi:10.1016/j.ydbio.2009.11.003.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Salminen M, Meyer BI, Bober E, Gruss P. Netrin 1 is required for semicircular canal formation in the mouse inner ear. Development. 2000;127(1):13–22.

    CAS  PubMed  Google Scholar 

  32. Chang W, Cole LK, Cantos R, Wu DK. Molecular genetics of vestibular organ development. In: Highstein SM et al., editors. Springer handbook of auditory research: the vestibular system, vol. 19. New York: Springer; 2003.

    Google Scholar 

  33. Kiernan AE, Pelling AL, Leung KK, Tang AS, Bell DM, Tease C, Lovell-Badge R, Steel KP, Cheah KS. Sox2 is required for sensory organ development in the mammalian inner ear. Nature. 2005;434(7036):1031–5.

    Article  CAS  PubMed  Google Scholar 

  34. Abraira VE, Del Rio T, Tucker AF, Slonimsky J, Keirnes HL, Goodrich LV. Cross-repressive interactions between Lrig3 and netrin1 shape the architecture of the inner ear. Development. 2008;135(24):4091–9. doi:10.1242/dev.029330.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Ponnio T, Burton Q, Pereira FA, Wu DK, Conneely OM. The nuclear receptor Nor-1 is essential for proliferation of the semicircular canals of the mouse inner ear. Mol Cell Biol. 2002;22(3):935–45.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Adams ME, Hurd EA, Beyer LA, Swiderski DL, Raphael Y, Martin DM. Defects in vestibular sensory epithelia and innervation in mice with loss of Chd7 function: implications for human CHARGE syndrome. J Comp Neurol. 2007;504(5):519–32.

    Article  PubMed  Google Scholar 

  37. Vervoort R, Ceulemans H, Van Aerschot L, D’Hooge R, David G. Genetic modification of the inner ear lateral semicircular canal phenotype of the Bmp4 haplo-insufficient mouse. Biochem Biophys Res Commun. 2010;394(3):780–5. doi:10.1016/j.bbrc.2010.03.069.

    Article  CAS  PubMed  Google Scholar 

  38. Kelly MW, Wu DK, Popper AN, Fay RR. Development of the inner ear. New York: Springer; 2005.

    Google Scholar 

  39. Morrison A, Hodgetts C, Gossler A, Lewis J. Expression of Delta1 and Serrate1 (Jag1) in the mouse inner ear. Mech Dev. 1999;84(1–2):169–72.

    Article  CAS  PubMed  Google Scholar 

  40. Shailam R, Landford PJ, Dolinsky CM, Norton CR, Gridley T, Kelley MW. Expression of proneural and neurogenic genes in the embryonic mammalian vestibular system. J Neurocytol. 1999;28(10–11):809–19.

    Article  CAS  PubMed  Google Scholar 

  41. Landford PJ, Shailam R, Norton CR, Gridley T, Kelley MW. Expression of Math1 and Hes5 in the cochleae of wildtype and Jag2 mutant mice. J Assoc Res Otolaryngol. 2000;1(2):161–71.

    Article  Google Scholar 

  42. Denman-Johnson K, Forge A. Establishment of hair bundle polarity and orientation in the developing vestibular system of the mouse. J Neurocytol. 1999;28(10–11):821–35.

    Article  CAS  PubMed  Google Scholar 

  43. Mbiene JP, Favre D, Sans A. The pattern of ciliary development in fetal mouse vestibular receptors. A qualitative and quantitative SEM study. Anat Embryol (Berl). 1984;170(3):229–38.

    Article  CAS  Google Scholar 

  44. Yin H, Copley CO, Goodrich LV, Deans MR. Comparison of phenotypes between different vangl2 mutants demonstrates dominant effects of the Looptail mutation during hair cell development. PLoS One. 2012;7(2):e31988. doi:10.1371/journal.pone.0031988.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Wang Y, Guo N, Nathans J. The role of Frizzled3 and Frizzled6 in neural tube closure and in the planar polarity of inner-ear sensory hair cells. J Neurosci. 2006;26(8):2147–56.

    Article  CAS  PubMed  Google Scholar 

  46. Jones C, Roper VC, Foucher I, Qian D, Banizs B, Petit C, et al. Ciliary proteins link basal body polarization to planar cell polarity regulation. Nat Genet. 2008;40(1):69–77.

    Article  CAS  PubMed  Google Scholar 

  47. Webb SW, Grillet N, Andrade LR, Xiong W, Swarthout L, Della Santina CC, et al. Regulation of PCDH15 function in mechanosensory hair cells by alternative splicing of the cytoplasmic domain. Development. 2011;138(8):1607–17. doi:10.1242/dev.060061.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Grimsley-Myers CM, Sipe CW, Geleoc GS, Lu X. The small GTPase Rac1 regulates auditory hair cell morphogenesis. J Neurosci. 2009;29(50):15859–69. doi:10.1523/JNEUROSCI.3998-09.2009.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Jaffe AB, Hall A. Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol. 2005;21:247–69.

    Article  CAS  PubMed  Google Scholar 

  50. Sipe CW, Lu X. Kif3a regulates planar polarization of auditory hair cells through both ciliary and non-ciliary mechanisms. Development. 2011;138(16):3441–9. doi:10.1242/dev.065961.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. Goetz SC, Anderson KV. The primary cilium: a signalling centre during vertebrate development. Nat Rev Genet. 2010;11(5):331–44. doi:10.1038/nrg2774.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Goodrich LV, Strutt D. Principles of planar polarity in animal development. Development. 2011;138(10):1877–92. doi:10.1242/dev.054080.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Klein TJ, Mlodzik M. Planar cell polarization: an emerging model points in the right direction. Annu Rev Cell Dev Biol. 2005;21:155–76.

    Article  CAS  PubMed  Google Scholar 

  54. Vladar EK, Antic D, Axelrod JD. Planar cell polarity signaling: the developing cell’s compass. Cold Spring Harb Perspect Biol. 2009;1(3):a002964. doi:10.1101/cshperspect.a002964.

    Article  PubMed Central  PubMed  Google Scholar 

  55. Montcouquiol M, Rachel RA, Lanford PJ, Copeland NG, Jenkins NA, Kelley MW. Identification of Vangl2 and Scrb1 as planar polarity genes in mammals. Nature. 2003;423(6936):173–7.

    Article  CAS  PubMed  Google Scholar 

  56. Curtin JA, Quint E, Tsipouri V, Arkell RM, Cattanach B, Copp AJ, et al. Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse. Curr Biol. 2003;13(13):1129–33.

    Article  CAS  PubMed  Google Scholar 

  57. Merchant SN, Nadol Jr. JB. Schuknecht’s pathology of the ear. 3rd ed. USA: PMPH; 2010.

    Google Scholar 

  58. Rosenbluth J. The fine structure of acoustic ganglia in the rat. J Cell Biol. 1962;12:329–59.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. D’Amico-Martel A, Noden DM. Contributions of placodal and neural crest cells to avian cranial peripheral ganglia. Am J Anat. 1983;166(4):445–68.

    Article  PubMed  Google Scholar 

  60. Harrison RG. Neuroblast versus sheath cell in the development of peripheral nerves. J Comp Neurol. 1924;37:123–205.

    Article  Google Scholar 

  61. Yntema CL. An experimental study on the origin of the sensory neurones and sheath cells of the IXth and Xth cranial nerves in Amblystoma punctatum. J Exp Zool. 1943;92:93–119.

    Article  Google Scholar 

  62. Breuskin I, Bodson M, Thelen N, Thiry M, Borgs L, Nguyen L, Stolt C, Wegner M, Lefebvre PP, Malgrange B. Glial but not neuronal development in the cochleo‐vestibular ganglion requires Sox10. J Neurochem. 2010;114(6):1827–39. doi:10.1111/j.1471-4159.2010.06897.x.

    Article  CAS  PubMed  Google Scholar 

  63. van Campenhout E. Experimental researches on the origin of the acoustic ganglion in amphibian embryos. J Exp Zool. 1935;72:175–93.

    Article  Google Scholar 

  64. Fritzsch B. Development of inner ear afferent connections: forming primary neurons and connecting them to the developing sensory epithelia. Brain Res Bull. 2003;60(5–6):423–33.

    Article  PubMed Central  PubMed  Google Scholar 

  65. Matei V, Pauley S, Kaing S, Rowitch D, Beisel KW, Morris K, Feng F, Jones K, Lee J, Fritzsch B. Smaller inner ear sensory epithelia in Neurog1 null mice are related to earlier hair cell cycle exit. Dev Dyn. 2005;234(3):633–50.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Corfas G, Velardez MO, Ko CP, Ratner N, Peles E. Mechanisms and roles of Axon–Schwann cell interactions. J Neurosci. 2004;24(42):9250–60.

    Article  CAS  PubMed  Google Scholar 

  67. Morris JK, Maklad A, Hansen LA, Feng F, Sorensen C, Lee KF, Macklin WB, Fritzsch B. A disorganized innervation of the inner ear persists in the absence of ErbB2. Brain Res. 2006;1091(1):186–99.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  68. Osborne NJ, Begbie J, Chilton JK, Schmidt H, Eickholt BJ. Semaphorin/neuropilin signaling influences the positioning of migratory neural crest cells within the hindbrain region of the chick. Dev Dyn. 2005;232(4):939–49.

    Article  CAS  PubMed  Google Scholar 

  69. Begbie J, Graham A. Integration between the epibranchial placodes and the hindbrain. Science. 2001;294(5542):595–8.

    Article  CAS  PubMed  Google Scholar 

  70. Freter S, Fleenor SJ, Freter R, Liu KJ, Begbie J. Cranial neural crest cells form corridors prefiguring sensory neuroblast migration. Development. 2013;140(17):3595–600. doi:10.1242/dev.091033.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  71. Yntema CL. Experiments on the origin of the sensory ganglia of the facial nerve in the chick. J Comp Neurol. 1944;81:147–67.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan

    Hiroko Torii & Akiko Taura

Authors
  1. Hiroko Torii
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akiko Taura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroko Torii .

Editor information

Editors and Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan

    Juichi Ito

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Japan

About this chapter

Cite this chapter

Torii, H., Taura, A. (2014). Vestibular Development. In: Ito, J. (eds) Regenerative Medicine for the Inner Ear. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54862-1_13

Download citation

  • DOI: https://doi.org/10.1007/978-4-431-54862-1_13

  • Published:

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-54861-4

  • Online ISBN: 978-4-431-54862-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation