Differentiation of mammalian vestibular hair cells from conditionally immortal, postnatal supporting cells

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Lawlor, P. ; Marcotti, W. ; Rivolta, M.N. ; Kros, C.J. ; Holley, M.C. (1999)
  • Publisher: HighWire

We provide evidence from a newly established, conditionally\ud 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\ud characteristic of supporting cells and two kinds of neonatal\ud hair cell. The cells expressed several characteristic features of normal hair cells, including the transcription factor Brn3.1, a functional acetylcholine receptor composed of a9 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 valuable in vitro preparation 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)
    56 references, page 1 of 6

    Adam J, Myat A, Roux IL, Eddison M, Henrique D, Ish-Horowicz D, Lewis J (1998) C ell fate choices and the expression of Notch, Delta and Serrate homologues in the chick inner ear: parallels with Drosophila sense-organ development. Development 125:4645- 4654.

    Alon U, Barkai N, Notterman DA, Gish K , Ybarra S, Mack D, Levine AJ (1999) Broad patterns of gene expression revealed by clustering analysis of tumor and normal colon tissues probed by oligonucleotide arrays. Proc Natl Acad Sci USA 96:6745- 6750.

    Baird R A, Steyger PS, Schuff N R (1996) Mitotic and nonmitotic hair cell regeneration in the bullfrog vestibular otolith organs. Ann N Y Acad Sci 781:59 -70.

    Barald K F, Lindberg K H, Hardiman K , Kavka AI, Lewis JE, Victor JC, Gardner CA, Poniatowski A (1997) Immortalised cell lines from embryonic avian and murine otocysts: tools for molecular studies of the developing inner ear. Int J Dev Neurosci 15:523-540.

    Chardin S, Romand R (1995) Regeneration and mammalian auditory hair cells. Science 267:707-711.

    Corwin J T, Cotanche DA (1988) Regeneration of sensory cells after acoustic trauma. Science 240:1772-1774.

    Cotanche DA, Lee K H, Stone JS, Picard DA (1994) Hair cell regeneration in the bird cochlea following noise damage or ototoxic drug damage. Anat Embryol 189:1-18.

    Elgoyhen AB, Johnson DS, Boulter J, Vetter DE, Heinemann S (1994) a9: an acetylcholine receptor with novel pharmacological properties expressed in rat cochlear hair cells. C ell 79:705-715.

    Erkman L, McEvilly RJ, L uo L, Ryan AK , Hooshmand F, O'Connell SM, Keithley EM, Rapaport DH, Ryan AF, Rosenfeld MG (1996) Role of transcription factors Brn-3.1 and Brn-3.2 in auditory and visual system development. Nature 381:603- 606.

    Fekete DM, Muthukumar S, Karagogeos D (1998) Hair cells and supporting cells share a common progenitor in the avian inner ear. J Neurosci 18:7811-7821.

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