Abstract
We provide evidence from a newly established, conditionally immortal cell line (UB/UE-1) that vestibular supporting cells from the mammalian inner ear can differentiate postnatally into more than one variant of hair cell. A clonal supporting cell line was established from pure utricular sensory epithelia of H2kbtsA58 transgenic mice 2 d after birth. Cell proliferation was dependent on conditional expression of the immortalizing gene, the “T” antigen from the SV40 virus. Proliferating cells expressed cytokeratins, and patch-clamp recordings revealed that they all expressed small membrane currents with little time-dependence. They stopped dividing within 2 d of being transferred to differentiating conditions, and within a week they formed three defined populations expressing membrane currents characteristic of supporting cells and two kinds of neonatal hair cell. The cells expressed several characteristic features of normal hair cells, including the transcription factor Brn3.1, a functional acetylcholine receptor composed of α9 subunits, and the cytoskeletal proteins myosin VI, myosin VIIa, and fimbrin. Immunofluorescence labeling and electron microscopy showed that the cells formed complex cytoskeletal arrays on their upper surfaces with structural features resembling those at the apices of normal hair cells. The cell line UB/UE-1 provides a valuablein vitropreparation in which the expression of numerous structural and physiological components can be initiated or upregulated during early stages of mammalian hair cell commitment and differentiation.
References
56
Referenced
41
10.1242/dev.125.23.4645
/ Development / Cell fate choices and the expression of Notch, Delta and Serrate homologues in the chick inner ear: parallels with Drosophila sense-organ development. by Adam (1998)10.1073/pnas.96.12.6745
10.1111/j.1749-6632.1996.tb15693.x
10.1016/S0736-5748(96)00108-6
10.1126/science.7839151
10.1126/science.3381100
10.1007/BF00193125
/ Anat Embryol / Hair cell regeneration in the bird cochlea following noise damage or ototoxic drug damage. by Cotanche (1994)10.1016/0092-8674(94)90555-X
10.1038/381603a0
10.1523/JNEUROSCI.18-19-07811.1998
10.1126/science.8456284
10.1002/(SICI)1096-9861(19980720)397:1<69::AID-CNE6>3.0.CO;2-G
10.1016/0301-0082(92)90003-W
10.1098/rspb.1995.0188
10.1007/BF00374185
10.1242/dev.125.23.4637
/ Development / Delta-Notch signalling and the patterning of sensory cell differentiation in the zebrafish ear: evidence from the mind bomb mutant. by Haddon (1998)10.1083/jcb.137.6.1287
10.1016/S0736-5748(96)00109-8
10.1152/jn.1995.73.4.1484
/ J Neurophysiol / Inwardly rectifying currents of saccular hair cells from the leopard frog. by Holt (1995)10.1007/s004240050873
10.1073/pnas.88.12.5096
10.1523/JNEUROSCI.16-02-00649.1996
10.1242/dev.119.4.1041
/ Development / The developing organ of Corti contains retinoic acid and forms supernumerary hair cells in response to exogenous retinoic acid in culture. by Kelley (1993)10.1523/JNEUROSCI.15-04-03013.1995
10.1038/362127a0
10.1016/0378-5955(92)90197-U
10.1038/227680a0
10.1038/6804
10.1152/jn.1989.62.4.935
/ J Neurophysiol / Studies of solitary semicircular canal hair cells in the adult pigeon. II. Voltage-dependent ionic conductances. by Lang (1989){'key': '2023041302432068000_19.21.9445.30', 'first-page': '41', 'article-title': 'Localization of the hair-cell-specific protein fimbrin during regeneration in the chicken cochlea.', 'volume': '1', 'author': 'Lee', 'year': '1996', 'journal-title': 'Audiol Neurootol'}
/ Audiol Neurootol / Localization of the hair-cell-specific protein fimbrin during regeneration in the chicken cochlea. by Lee (1996)10.1126/science.8480180
10.1016/S0925-4773(98)00165-8
10.1097/00001756-199902250-00029
/ NeuroReport / Position-dependent expression of inwardly rectifying K+ currents by hair cells of frog semicircular canals. by Marcotti (1999)10.1152/jn.1997.78.4.1913
/ J Neurophysiol / Electrophysiological properties of vestibular sensory and supporting cells in the labyrinth slice before and during regeneration. by Masetto (1997)10.1152/jn.1994.72.1.443
/ J Neurophysiol / Differential expression of potassium currents by hair cells in thin slices of frog crista ampullaris. by Masetto (1994)10.1002/(SICI)1096-9861(19980525)395:1<18::AID-CNE2>3.0.CO;2-K
10.1113/jphysiol.1984.sp015218
10.1016/0378-5955(94)90002-7
10.1016/0378-5955(90)90135-C
10.1152/jn.1994.71.1.317
/ J Neurophysiol / Potassium currents in mammalian and avian isolated type I semicircular canal hair cells. by Rennie (1994)10.1113/jphysiol.1987.sp016509
10.1098/rspb.1998.0477
/ Proc R Soc Lond B Biol Sci / Auditory hair cell progenitors immortalised from the mammalian inner ear. by Rivolta (1998)10.1152/jn.1996.76.2.995
/ J Neurophysiol / A delayed rectifier conductance in type I hair cells of the mouse utricle. by Rüsch (1996)10.1523/JNEUROSCI.18-18-07474.1998
10.1126/science.3381101
10.1016/0378-5955(95)00228-6
10.1002/cne.902060102
-
Slepecky N (1996) Structure of the mammalian cochlea. in Handbook of auditory research, Vol VIII, The cochlea, eds Dallos P Popper AN Fay RR (Springer, New York), pp 44–129.
(
10.1007/978-1-4612-0757-3_2
) 10.1097/00019052-199802000-00004
10.1242/dev.126.5.961
/ Development / Delta1 expression during avian hair cell regeneration. by Stone (1999)10.1113/jphysiol.1996.sp021624
10.1126/science.283.5398.83
10.1126/science.8456285
10.1073/pnas.94.17.9445
10.1242/dev.125.20.3935
/ Development / Requirement for brn-3c in maturation and survival, but not in fate determination of inner ear hair cells. by Xiang (1998)10.1016/S0378-5955(97)00205-0
Dates
Type | When |
---|---|
Created | 7 years, 5 months ago (April 3, 2018, 10:20 p.m.) |
Deposited | 2 years, 4 months ago (April 13, 2023, 8:59 a.m.) |
Indexed | 1 year, 3 months ago (May 17, 2024, 9:39 a.m.) |
Issued | 25 years, 10 months ago (Nov. 1, 1999) |
Published | 25 years, 10 months ago (Nov. 1, 1999) |
Published Online | 25 years, 10 months ago (Nov. 1, 1999) |
Published Print | 25 years, 10 months ago (Nov. 1, 1999) |
@article{Lawlor_1999, title={Differentiation of Mammalian Vestibular Hair Cells from Conditionally Immortal, Postnatal Supporting Cells}, volume={19}, ISSN={1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.19-21-09445.1999}, DOI={10.1523/jneurosci.19-21-09445.1999}, number={21}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Lawlor, Patrick and Marcotti, Walter and Rivolta, Marcelo N. and Kros, Corné J. and Holley, Matthew C.}, year={1999}, month=nov, pages={9445–9458} }