• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Apr 11, 1995; 92(8): 3152–3155.

Induction of cell proliferation in mammalian inner-ear sensory epithelia by transforming growth factor alpha and epidermal growth factor.


Regenerative proliferation occurs in the inner-ear sensory epithelial of warm-blooded vertebrates after insult. To determine how this proliferation is controlled in the mature mammalian inner ear, several growth factors were tested for effects on progenitor-cell division in cultured mouse vestibular sensory epithelia. Cell proliferation was induced in the sensory epithelium by transforming growth factor alpha (TGF-alpha) in a dose-dependent manner. Proliferation was also induced by epidermal growth factor (EGF) when supplemented with insulin, but not EGF alone. These observations suggest that stimulation of the EGF receptors by TGF-alpha binding, or EGF (plus insulin) binding, stimulates cell proliferation in the mature mammalian vestibular sensory epithelium.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Cotanche DA. Regeneration of hair cell stereociliary bundles in the chick cochlea following severe acoustic trauma. Hear Res. 1987;30(2-3):181–195. [PubMed]
  • Corwin JT, Cotanche DA. Regeneration of sensory hair cells after acoustic trauma. Science. 1988 Jun 24;240(4860):1772–1774. [PubMed]
  • Ryals BM, Rubel EW. Hair cell regeneration after acoustic trauma in adult Coturnix quail. Science. 1988 Jun 24;240(4860):1774–1776. [PubMed]
  • Cruz RM, Lambert PR, Rubel EW. Light microscopic evidence of hair cell regeneration after gentamicin toxicity in chick cochlea. Arch Otolaryngol Head Neck Surg. 1987 Oct;113(10):1058–1062. [PubMed]
  • Lombarte A, Yan HY, Popper AN, Chang JS, Platt C. Damage and regeneration of hair cell ciliary bundles in a fish ear following treatment with gentamicin. Hear Res. 1993 Jan;64(2):166–174. [PubMed]
  • Baird RA, Torres MA, Schuff NR. Hair cell regeneration in the bullfrog vestibular otolith organs following aminoglycoside toxicity. Hear Res. 1993 Feb;65(1-2):164–174. [PubMed]
  • Henry WJ, Makaretz M, Saunders JC, Schneider ME, Vrettakos P. Hair cell loss and regeneration after exposure to intense sound in neonatal chicks. Otolaryngol Head Neck Surg. 1988 Jun;98(6):607–611. [PubMed]
  • Weisleder P, Rubel EW. Hair cell regeneration after streptomycin toxicity in the avian vestibular epithelium. J Comp Neurol. 1993 May 1;331(1):97–110. [PubMed]
  • Hashino E, Sokabe M. Kanamycin induced low-frequency hearing loss in the budgerigar (Melopsittacus undulatus). J Acoust Soc Am. 1989 Jan;85(1):289–294. [PubMed]
  • Duckert LG, Rubel EW. Ultrastructural observations on regenerating hair cells in the chick basilar papilla. Hear Res. 1990 Sep;48(1-2):161–182. [PubMed]
  • Tucci DL, Rubel EW. Physiologic status of regenerated hair cells in the avian inner ear following aminoglycoside ototoxicity. Otolaryngol Head Neck Surg. 1990 Sep;103(3):443–450. [PubMed]
  • Cotanche DA, Corwin JT. Stereociliary bundles reorient during hair cell development and regeneration in the chick cochlea. Hear Res. 1991 Apr;52(2):379–402. [PubMed]
  • Hashino E, Tanaka Y, Sokabe M. Hair cell damage and recovery following chronic application of kanamycin in the chick cochlea. Hear Res. 1991 Apr;52(2):356–368. [PubMed]
  • Lippe WR, Westbrook EW, Ryals BM. Hair cell regeneration in the chicken cochlea following aminoglycoside toxicity. Hear Res. 1991 Nov;56(1-2):203–210. [PubMed]
  • Duckert LG, Rubel EW. Morphological correlates of functional recovery in the chicken inner ear after gentamycin treatment. J Comp Neurol. 1993 May 1;331(1):75–96. [PubMed]
  • Hashino E, Tanaka Y, Salvi RJ, Sokabe M. Hair cell regeneration in the adult budgerigar after kanamycin ototoxicity. Hear Res. 1992 Apr;59(1):46–58. [PubMed]
  • Jones TA, Nelson RC. Recovery of vestibular function following hair cell destruction by streptomycin. Hear Res. 1992 Oct;62(2):181–186. [PubMed]
  • Ryals BM, Westbrook EW, Stoots S, Spencer RF. Changes in the acoustic nerve after hair cell regeneration. Exp Neurol. 1992 Jan;115(1):18–22. [PubMed]
  • Marean GC, Burt JM, Beecher MD, Rubel EW. Hair cell regeneration in the European starling (Sturnus vulgaris): recovery of pure-tone detection thresholds. Hear Res. 1993 Dec;71(1-2):125–136. [PubMed]
  • Girod DA, Duckert LG, Rubel EW. Possible precursors of regenerated hair cells in the avian cochlea following acoustic trauma. Hear Res. 1989 Nov;42(2-3):175–194. [PubMed]
  • Balak KJ, Corwin JT, Jones JE. Regenerated hair cells can originate from supporting cell progeny: evidence from phototoxicity and laser ablation experiments in the lateral line system. J Neurosci. 1990 Aug;10(8):2502–2512. [PubMed]
  • Raphael Y. Evidence for supporting cell mitosis in response to acoustic trauma in the avian inner ear. J Neurocytol. 1992 Sep;21(9):663–671. [PubMed]
  • Warchol ME, Lambert PR, Goldstein BJ, Forge A, Corwin JT. Regenerative proliferation in inner ear sensory epithelia from adult guinea pigs and humans. Science. 1993 Mar 12;259(5101):1619–1622. [PubMed]
  • Rubel EW, Dew LA, Roberson DW. Mammalian vestibular hair cell regeneration. Science. 1995 Feb 3;267(5198):701–707. [PubMed]
  • Forge A, Li L, Corwin JT, Nevill G. Ultrastructural evidence for hair cell regeneration in the mammalian inner ear. Science. 1993 Mar 12;259(5101):1616–1619. [PubMed]
  • Roberson DW, Rubel EW. Cell division in the gerbil cochlea after acoustic trauma. Am J Otol. 1994 Jan;15(1):28–34. [PubMed]
  • Represa JJ, Miner C, Barbosa E, Giraldez F. Bombesin and other growth factors activate cell proliferation in chick embryo otic vesicles in culture. Development. 1988 May;103(1):87–96. [PubMed]
  • Represa J, León Y, Miner C, Giraldez F. The int-2 proto-oncogene is responsible for induction of the inner ear. Nature. 1991 Oct 10;353(6344):561–563. [PubMed]
  • Oesterle EC, Tsue TT, Reh TA, Rubel EW. Hair-cell regeneration in organ cultures of the postnatal chicken inner ear. Hear Res. 1993 Oct;70(1):85–108. [PubMed]
  • Marquardt H, Hunkapiller MW, Hood LE, Todaro GJ. Rat transforming growth factor type 1: structure and relation to epidermal growth factor. Science. 1984 Mar 9;223(4640):1079–1082. [PubMed]
  • De Larco JE, Todaro GJ. Sarcoma growth factor (SGF): specific binding to epidermal growth factor (EGF) membrane receptors. J Cell Physiol. 1980 Feb;102(2):267–277. [PubMed]
  • Pike LJ, Marquardt H, Todaro GJ, Gallis B, Casnellie JE, Bornstein P, Krebs EG. Transforming growth factor and epidermal growth factor stimulate the phosphorylation of a synthetic, tyrosine-containing peptide in a similar manner. J Biol Chem. 1982 Dec 25;257(24):14628–14631. [PubMed]
  • Katayama A, Corwin JT. Cochlear cytogenesis visualized through pulse labeling of chick embryos in culture. J Comp Neurol. 1993 Jul 1;333(1):28–40. [PubMed]
  • Tsue TT, Watling DL, Weisleder P, Coltrera MD, Rubel EW. Identification of hair cell progenitors and intermitotic migration of their nuclei in the normal and regenerating avian inner ear. J Neurosci. 1994 Jan;14(1):140–152. [PubMed]
  • Schultz GS, White M, Mitchell R, Brown G, Lynch J, Twardzik DR, Todaro GJ. Epithelial wound healing enhanced by transforming growth factor-alpha and vaccinia growth factor. Science. 1987 Jan 16;235(4786):350–352. [PubMed]
  • Anchan RM, Reh TA, Angello J, Balliet A, Walker M. EGF and TGF-alpha stimulate retinal neuroepithelial cell proliferation in vitro. Neuron. 1991 Jun;6(6):923–936. [PubMed]
  • Lillien L, Cepko C. Control of proliferation in the retina: temporal changes in responsiveness to FGF and TGF alpha. Development. 1992 May;115(1):253–266. [PubMed]
  • Reynolds BA, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science. 1992 Mar 27;255(5052):1707–1710. [PubMed]
  • Massagué J. Transforming growth factor-alpha. A model for membrane-anchored growth factors. J Biol Chem. 1990 Dec 15;265(35):21393–21396. [PubMed]
  • Wilcox JN, Derynck R. Developmental expression of transforming growth factors alpha and beta in mouse fetus. Mol Cell Biol. 1988 Aug;8(8):3415–3422. [PMC free article] [PubMed]
  • Lambert PR. Inner ear hair cell regeneration in a mammal: identification of a triggering factor. Laryngoscope. 1994 Jun;104(6 Pt 1):701–718. [PubMed]
  • Ebner R, Derynck R. Epidermal growth factor and transforming growth factor-alpha: differential intracellular routing and processing of ligand-receptor complexes. Cell Regul. 1991 Aug;2(8):599–612. [PMC free article] [PubMed]
  • Roberson DF, Weisleder P, Bohrer PS, Rubel EW. Ongoing production of sensory cells in the vestibular epithelium of the chick. Hear Res. 1992 Jan;57(2):166–174. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...