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MeSH Review

Otolithic Membrane

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Disease relevance of Otolithic Membrane


High impact information on Otolithic Membrane

  • The present study used the C57BL6JEi-het mouse strain (het), which lacks macular otoconia, to elucidate the contribution of specific vestibular receptors [4].
  • 5. The encoded 95-kDa glycoprotein is the major protein of the utricular and saccular otoconia and thus was named otoconin-95 [5].
  • To begin to elucidate these mechanisms, we have partially sequenced and cloned the major protein component of murine otoconia, otoconin-90 (OC90) [6].
  • In mammals, otoconia are composed of proteins (otoconins) and calcium carbonate crystals in a calcite lattice [6].
  • These results suggest that ROS generated by a Noxo1-dependent vestibular oxidase are critical for otoconia formation and may be required for interactions among otoconial components [7].

Biological context of Otolithic Membrane

  • Here we investigated the compensatory eye movements in tilted mice, which lack otoconia because of a mutation in otopetrin 1 [8].
  • The precursor cells subsequently converge at the midline after neurulation and undergo cell interactions that decide the fates of the otolith and ocellus [9].
  • To test this hypothesis, we selectively stimulated otolith and body graviceptors sinusoidally along different head axes in the coronal plane with off-vertical axis rotation (OVAR) and recorded sympathetic efferent activity in the peroneal nerve (muscle sympathetic nerve activity, MSNA), blood pressure, heart rate, and respiratory rate [10].
  • Our findings suggest that Trk receptors and their cognate neurotrophins in central otolith neurons may contribute to the modulation of gravity-related spatial information during horizontal head movements [11].
  • NOX3 is almost exclusively expressed in the inner ear, where it is involved in otoconia morphogenesis, but based on its localization might also play a role in the auditory system [12].

Anatomical context of Otolithic Membrane

  • Nox3, a member of the superoxide-producing NADPH oxidase (Nox) family, participates in otoconia formation in mouse inner ears, which is required for perception of balance and gravity [13].
  • Vestibular identity was based on: (1) stereociliary bundle morphology; (2) spacing of hair cells and supporting cells; (3) the presence of otoliths; (4) immunolabeling indicative of vestibular supporting cells; and (5) expression of Msx1, a marker of certain vestibular sensory organs [14].
  • In hybrid embryos, antisense FH1 ODNs blocked restoration of the otolith, notochord, and tail, reverting the larva back to the anural state [15].
  • Our findings suggest that NMDA-type ionotropic glutamate receptors play a key role in the OVAR-induced neuronal activation of the vestibular nuclei, thus providing a morphological basis for further study of glutamatergic central otolith neurons and their involvement in sensorimotor regulation and autonomic functions of rats [16].
  • 1. The electrical activity of single trochlear motoneurons (TMns) and axons of second order vestibular neurons presumably terminating on these motoneurons were studied during natural stimulation of semicircular canals and otolith organs in cats anesthetized with Ketamine [17].

Associations of Otolithic Membrane with chemical compounds

  • Motile hairs on the cyst's luminal surface moved as rods through +/- 10 degrees Hz when free and at 7 Hz when loaded with the weight of the statoconia (at 120 degrees C) [18].
  • Nicotine-induced nystagmus was detected in 27 subjects (51%); in 25 of these (93%) it was modulated by otolith input [19].
  • Melanin formation in both the otolith and the ocellus of PTU-treated larvae at 12 hours of development was completely inhibited [20].
  • Unilateral sodium arsanilate labyrinthectomies (UL) were performed either 24 h (acute) or 2 wk (chronic) before exposure to a 90 min, 2-G centripetal acceleration along the interaural axis that stimulated the intact otolith organs [21].
  • Packing of fibrils is tighter after phosphotungstic acid (PTA) stained otoconia than with other histochemical stains, which usually produce looser packing of fibrils and seemingly larger central core [22].

Gene context of Otolithic Membrane

  • Here we show that the zebrafish, Danio rerio, contains a highly conserved gene, otop1, that is essential for otolith formation [23].
  • Otolith matrix proteins OMP-1 and Otolin-1 are necessary for normal otolith growth and their correct anchoring onto the sensory maculae [24].
  • We examined the localization of Starmaker, a secreted protein that is highly abundant in otoliths in backstroke mutants [25].
  • In lm mice, which have absent otoconia in the utricle and a variable loss of otoconia in the saccule, VsEPs were present and average P1/N1 amplitudes were highly correlated with the average loss of saccular otoconia (R = 0.77,p < 0.001) [26].
  • These data demonstrate that PMCA2 is required for both balance and hearing and suggest that it may be a major source of the calcium used in the formation and maintenance of otoconia [27].

Analytical, diagnostic and therapeutic context of Otolithic Membrane


  1. A mathematical model for top-shelf vertigo: the role of sedimenting otoconia in BPPV. Squires, T.M., Weidman, M.S., Hain, T.C., Stone, H.A. Journal of biomechanics. (2004) [Pubmed]
  2. Vestibular evoked myogenic potentials in ipsilateral delayed endolymphatic hydrops. Ohki, M., Matsuzaki, M., Sugasawa, K., Murofushi, T. ORL J. Otorhinolaryngol. Relat. Spec. (2002) [Pubmed]
  3. Calbindin and calmodulin localization in the developing vestibular organ of the musk shrew (Suncus murinus). Karita, K., Nishizaki, K., Nomiya, S., Masuda, Y. Acta oto-laryngologica. Supplementum. (1999) [Pubmed]
  4. Neurovestibular modulation of circadian and homeostatic regulation: vestibulohypothalamic connection? Fuller, P.M., Jones, T.A., Jones, S.M., Fuller, C.A. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  5. Characterization of otoconin-95, the major protein of murine otoconia, provides insights into the formation of these inner ear biominerals. Verpy, E., Leibovici, M., Petit, C. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  6. Otoconin-90, the mammalian otoconial matrix protein, contains two domains of homology to secretory phospholipase A2. Wang, Y., Kowalski, P.E., Thalmann, I., Ornitz, D.M., Mager, D.L., Thalmann, R. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  7. Inactivation of NADPH oxidase organizer 1 results in severe imbalance. Kiss, P.J., Knisz, J., Zhang, Y., Baltrusaitis, J., Sigmund, C.D., Thalmann, R., Smith, R.J., Verpy, E., Bánfi, B. Curr. Biol. (2006) [Pubmed]
  8. Otolith deprivation induces optokinetic compensation. Andreescu, C.E., De Ruiter, M.M., De Zeeuw, C.I., De Jeu, M.T. J. Neurophysiol. (2005) [Pubmed]
  9. Evolution and development of brain sensory organs in molgulid ascidians. Jeffery, W.R. Evol. Dev. (2004) [Pubmed]
  10. Vestibular control of sympathetic activity. An otolith-sympathetic reflex in humans. Kaufmann, H., Biaggioni, I., Voustianiouk, A., Diedrich, A., Costa, F., Clarke, R., Gizzi, M., Raphan, T., Cohen, B. Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. (2002) [Pubmed]
  11. Expression of Trk receptors in otolith-related neurons in the vestibular nucleus of rats. Zhang, F.X., Lai, C.H., Tse, Y.C., Shum, D.K., Chan, Y.S. Brain Res. (2005) [Pubmed]
  12. Tissue distribution and putative physiological function of NOX family NADPH oxidases. Krause, K.H. Jpn. J. Infect. Dis. (2004) [Pubmed]
  13. The NADPH oxidase Nox3 constitutively produces superoxide in a p22phox-dependent manner: its regulation by oxidase organizers and activators. Ueno, N., Takeya, R., Miyano, K., Kikuchi, H., Sumimoto, H. J. Biol. Chem. (2005) [Pubmed]
  14. Forced activation of Wnt signaling alters morphogenesis and sensory organ identity in the chicken inner ear. Stevens, C.B., Davies, A.L., Battista, S., Lewis, J.H., Fekete, D.M. Dev. Biol. (2003) [Pubmed]
  15. The forkhead gene FH1 is involved in evolutionary modification of the ascidian tadpole larva. Olsen, C.L., Natzle, J.E., Jeffery, W.R. Mech. Dev. (1999) [Pubmed]
  16. Quantitative study of the coexpression of Fos and N-methyl-D aspartate (NMDA) receptor subunits in otolith-related vestibular nuclear neurons of rats. Chen, L.W., Lai, C.H., Law, H.Y., Yung, K.K., Chan, Y.S. J. Comp. Neurol. (2003) [Pubmed]
  17. Response characteristics of semicircular canal and otolith systems in cat. II. Responses of trochlear motoneurons. Blanks, R.H., Anderson, J.H., Precht, W. Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. (1978) [Pubmed]
  18. A common origin of voltage noise and generator potentials in statocyst hair cells. Grossman, Y., Alkon, D.L., Heldman, E. J. Gen. Physiol. (1979) [Pubmed]
  19. Nicotine-induced nystagmus: three-dimensional analysis and dependence on head position. Pereira, C.B., Strupp, M., Eggert, T., Straube, A., Brandt, T. Neurology (2000) [Pubmed]
  20. The role of pigment cells in the brain of ascidian larva. Sakurai, D., Goda, M., Kohmura, Y., Horie, T., Iwamoto, H., Ohtsuki, H., Tsuda, M. J. Comp. Neurol. (2004) [Pubmed]
  21. Otolith-brain stem connectivity: evidence for differential neural activation by vestibular hair cells based on quantification of FOS expression in unilateral labyrinthectomized rats. Kaufman, G.D., Anderson, J.H., Beitz, A.J. J. Neurophysiol. (1993) [Pubmed]
  22. High resolution and image processing of otoconia matrix. Fermin, C.D. Microsc. Res. Tech. (1993) [Pubmed]
  23. Otopetrin 1 is required for otolith formation in the zebrafish Danio rerio. Hughes, I., Blasiole, B., Huss, D., Warchol, M.E., Rath, N.P., Hurle, B., Ignatova, E., Dickman, J.D., Thalmann, R., Levenson, R., Ornitz, D.M. Dev. Biol. (2004) [Pubmed]
  24. Otolith matrix proteins OMP-1 and Otolin-1 are necessary for normal otolith growth and their correct anchoring onto the sensory maculae. Murayama, E., Herbomel, P., Kawakami, A., Takeda, H., Nagasawa, H. Mech. Dev. (2005) [Pubmed]
  25. Mutated otopetrin 1 affects the genesis of otoliths and the localization of Starmaker in zebrafish. Söllner, C., Schwarz, H., Geisler, R., Nicolson, T. Dev. Genes Evol. (2004) [Pubmed]
  26. Gravity receptor function in mice with graded otoconial deficiencies. Jones, S.M., Erway, L.C., Johnson, K.R., Yu, H., Jones, T.A. Hear. Res. (2004) [Pubmed]
  27. Balance and hearing deficits in mice with a null mutation in the gene encoding plasma membrane Ca2+-ATPase isoform 2. Kozel, P.J., Friedman, R.A., Erway, L.C., Yamoah, E.N., Liu, L.H., Riddle, T., Duffy, J.J., Doetschman, T., Miller, M.L., Cardell, E.L., Shull, G.E. J. Biol. Chem. (1998) [Pubmed]
  28. Differential effect of the loop diuretic furosemide on short latency auditory and vestibular-evoked potentials. Freeman, S., Plotnik, M., Elidan, J., Sohmer, H. The American journal of otology. (1999) [Pubmed]
  29. Analysis of the soluble matrix of vaterite otoliths of juvenile herring (Clupea harengus): do crystalline otoliths have less protein? Tomás, J., Geffen, A.J., Allen, I.S., Berges, J. Comp. Biochem. Physiol., Part A Mol. Integr. Physiol. (2004) [Pubmed]
  30. Otoconia on the vestibular dark cells of the ampullar areas. Fujii, M., Harada, Y., Hirakawa, K., Takumida, M. Acta oto-laryngologica. Supplementum. (1995) [Pubmed]
  31. Studies of otoconia in the developing chick by polarized light microscopy. Ballarino, J., Howland, H.C., Skinner, H.C., Brothers, E.B., Bassett, W. Am. J. Anat. (1985) [Pubmed]
  32. Uptake of tetracycline in otoconia of the guinea pig. Zhang, D.M., Takumida, M., Harada, Y. Acta Otolaryngol. (1996) [Pubmed]
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