Proliferative generation of mammalian auditory hair cells in culture.
Hair cell (HC) and supporting cell (SC) productions are completed during early embryonic development of the mammalian cochlea. This study shows that acutely dissociated cells from the newborn rat organ of Corti, developed into so-called otospheres consisting of 98% nestin (+) cells when plated on a non-adherent substratum in the presence of either epidermal growth factor (EGF) or fibroblast growth factor (FGF2). Within cultured otospheres, nestin (+) cells were shown to express EGF receptor (EGFR) and FGFR2 and rapidly give rise to newly formed myosin VIIA (+) HCs and p27(KIP1) (+) SCs. Myosin VIIA (+) HCs had incorporated bromodeoxyuridine (BrdU) demonstrating that they were generated by a mitotic process. Ultrastructural studies confirmed that HCs had differentiated within the otosphere, as defined by the presence of both cuticular plates and stereocilia. This work raises the hypothesis that nestin (+) cells might be a source of newly generated HCs and SCs in the injured postnatal organ of Corti.
Malgrange
Brigitte
B
Center for Cellular and Molecular Neurobiology, University of Liège, 17 Place Delcour, B-4020, Liège, Belgium. bmalgrange@ulg.ac.be
Belachew
Shibeshih
S
Thiry
Marc
M
Nguyen
Laurent
L
Rogister
Bernard
B
Alvarez
Maria-Luz
ML
Rigo
Jean-Michel
JM
Van De Water
Thomas R
TR
Moonen
Gustave
G
Lefebvre
Philippe P
PP
D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004398:Dyneins; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000166:cytology* / Q000378:metabolism*; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008938:Mitosis; D000081412:Myosin VIIa; D009218:Myosins / Q000378:metabolism; D009419:Nerve Tissue Proteins; D064231:Nestin; D009925:Organ of Corti / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000378:metabolism
C493962:Cdkn1b protein, rat; D018797:Cell Cycle Proteins; D007381:Intermediate Filament Proteins; C000631457:Myo7a protein, rat; D000081412:Myosin VIIa; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D017468:Receptors, Fibroblast Growth Factor; D025521:Tumor Suppressor Proteins; D016222:Fibroblast Growth Factor 2; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; C496356:Fgfr2 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D009218:Myosins; D004398:Dyneins; D001973:Bromodeoxyuridine