1. MRC Institute of Hearing Research, University of Nottingham, Nottingham NG7 2RD, UK
2. Department of Biochemistry, The University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong, China
3. Division of Developmental Genetics, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
4. MRC Mammalian Genetics Unit, Harwell, Didcot OX11 ORD, UK
5. These authors contributed equally to this work
6. Present addresses: The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA (A.E.K.); Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK (K.P.S.); Science Style, Courtland Road, Oxford OX4 4JB, UK (C.T.)

Correspondence to: Kathryn S. E. Cheah² Correspondence and requests for materials should be addressed to K.S.E.C. (Email: hrmbdkc@hkusua.hku.hk).

Abstract

Sensory hair cells and their associated non-sensory supporting cells in the inner ear are fundamental for hearing and balance. They arise from a common progenitor¹, but little is known about the molecular events specifying this cell lineage. We recently identified two allelic mouse mutants, light coat and circling (Lcc) and yellow submarine (Ysb), that show hearing and balance impairment². Lcc/Lcc mice are completely deaf, whereas Ysb/Ysb mice are severely hearing impaired². We report here that inner ears of Lcc/Lcc mice fail to establish a prosensory domain and neither hair cells nor supporting cells differentiate, resulting in a severe inner ear malformation, whereas the sensory epithelium of Ysb/Ysb mice shows abnormal development with disorganized and fewer hair cells. These phenotypes are due to the absence (in Lcc mutants) or reduced expression (in Ysb mutants) of the transcription factor SOX2, specifically within the developing inner ear. SOX2 continues to be expressed in the inner ears of mice lacking Math1 (also known as Atoh1 and HATH1), a gene essential for hair cell differentiation, whereas Math1 expression is absent in Lcc mutants, suggesting that Sox2 acts upstream of Math1.

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.