1Anna L. Pelling, 2,4Amy Kiernan, 1Keith K.H. Leung, 1Anna S.P. Tang, 3Donald M. Bell, 3Robin Lovell-Badge, 2,5Karen Steel, 1Kathryn S.E. Cheah
1The University of Hong Kong, Department of Biochemistry, Faculty of Medicine Building, 21 Sassoon Rd, Hong Kong, China, 2MRC Institute For Hearing Research, University of Nottingham, Nottingham, NG7 2RD, UK, 3National Institute for Medical Research, Division of Developmental Genetics, The Ridgeway, Mill Hill, London, NW7 1AA, UK, 4Jackson Laboratory, 600 Main St., Bar Harbor, ME 04609, USA, 5Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK
Inner ear sensory hair cells and their associated non-sensory supporting cells are fundamental for hearing and balance. They arise from a common progenitor, but little is known about the molecular events that specify this cell lineage. We recently identified two allelic mouse mutants, Light coat and circling (lcc) and Yellow submarine (ysb) that show hearing defects and balance impairment. lcc/lcc mice are completely deaf while ysb/ysb are severely hearing impaired. We have shown that lcc/lcc inner ears fail to establish a prosensory domain and neither hair cells nor supporting cells differentiate, resulting in a severe inner ear malformation, whereas the ysb/ysb inner ear sensory epithelia show abnormal development with disorganised and fewer hair cells. These phenotypes are due, respectively, to the inner ear specific absence or reduced expression of the transcription factor Sox2 during embryonic development. Sox2 continues to be expressed in the inner ears of mice lacking Atoh1, a gene essential for hair cell differentiation, whereas Atoh1 expression is absent in lcc mutants, suggesting Sox2 acts upstream of Atoh1.
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