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The winged helix transcription factor Fkh10 is required for normal development of the inner ear

Nature Genetics volume 20, pages 374–376 (1998)Cite this article

Abstract

Fkh10 is a member of the forkhead family of winged helix transcriptional regulators. Genes encoding forkhead proteins are instrumental during embryogenesis in mammals, in particular during development of the nervous system 1, 2, 3, 4, 5 . Here we report that mice with a targeted disruption of the Fkh10 locus exhibit circling behaviour, poor swimming ability and abnormal reaching response—all common findings in mice with vestibular dysfunction 6 . These animals also fail to elicit a Preyer reflex in response to a suprathreshold auditory stimulation, as seen in mice with profound hearing impairment 7, 8 . Histological examination of the inner ear reveals a gross structural malformation of the vestibulum as well as the cochlea. These structures have been replaced by a single irregular cavity in which neither proper semicircular ducts nor cochlea can be identified. We also show that at 9.5 days post coitum (dpc), Fkh10 is exclusively expressed in the otic vesicle. These findings implicate Fkh10 as an early regulator necessary for development of both cochlea and vestibulum and identify its human homologue FKHL10 as a previously unknown candidate deafness gene at 5q34.

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Figure 1: Targeting of Fkh10 in R1 ES cells.
Figure 2: Histological sections of the inner ear.
Figure 3: Expression of Fkh10 during embryonic development.

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Acknowledgements

We thank A. Gossler, K.R. Johnson and L.P. Kozak for valuable discussion and A. Lindahl for help in analysing serum samples. This work was made possible with support from the Swedish Medical Research Council, The Lundberg Foundation, The Juvenile Diabetes Foundation, a Junior Individual Grant from The Swedish Foundation for Strategic Research to S.E. and an EMBO short term fellowship to M.H.

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Authors and Affiliations

  1. Department of Molecular Biology, The Lundberg Laboratory, Göteborg University, Box 462, Göteborg, SE 405 30, Sweden

    Malin Hulander, Peter Carlsson & Sven Enerbäck.

  2. Max Planck Institute of Psychiatry, Kraepleinstr, Munich, 2–10, D-80804, Germany

    Wolfgang Wurst

  3. Department of Physical Chemistry, The Unit for Biotechnology, Chalmers University of Technology, Göteborg, SE 412 96, Sweden

    Sven Enerbäck.

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  1. Malin Hulander
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Correspondence to Sven Enerbäck..

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Hulander, M., Wurst, W., Carlsson, P. et al. The winged helix transcription factor Fkh10 is required for normal development of the inner ear. Nat Genet 20, 374–376 (1998). https://doi.org/10.1038/3850

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