Requirement for Brn-3c in maturation and survival, but not in fate determination of inner ear hair cells.
Mutations in the POU domain gene Brn-3c causes hearing impairment in both the human and mouse as a result of inner ear hair cell loss. We show here that during murine embryogenesis, Brn-3c is expressed in postmitotic cells committed to hair cell phenotype but not in mitotic progenitors in the inner ear sensory epithelium. In developing auditory and vestibular sensory epithelia of Brn-3c-/- mice, hair cells are found to be generated and undergo initial differentiation as indicated by their morphology, laminar position and expression of hair cell markers, including myosins VI and VIIa, calretinin and parvalbumin. However, a small number of hair cells are anomalously retained in the supporting cell layer in the vestibular sensory epithelia. Furthermore, the initially differentiated hair cells fail to form stereociliary bundles and degenerate by apoptosis in the Brn-3c-/- mice. These data indicate a crucial role for Brn-3c in maturation, survival and migration of hair cells, but not in proliferation or commitment of hair cell progenitors.
Xiang
M
M
Center for Advanced Biotechnology and Medicine, Department of Pediatrics, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA. xiang@mbcl.rutgers.edu.
Gao
W Q
WQ
Hasson
T
T
Shin
J J
JJ
D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation; D002465:Cell Movement; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004432:Ear, Middle / Q000166:cytology / Q000196:embryology*; D004847:Epithelial Cells / Q000166:cytology; D017950:Ganglia, Sensory / Q000166:cytology; D015870:Gene Expression; D006199:Hair Cells, Auditory, Inner / Q000166:cytology* / Q000196:embryology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis; D013234:Stem Cells / Q000166:cytology; D050818:Transcription Factor Brn-3; D050821:Transcription Factor Brn-3C; D014157:Transcription Factors / Q000378:metabolism*
D015415:Biomarkers; D004268:DNA-Binding Proteins; D050818:Transcription Factor Brn-3; D050821:Transcription Factor Brn-3C; D014157:Transcription Factors