International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


ORAL PRESENTATION

THURSDAY OCTOBER 21

2.30pm – 2.45pm

MUTANT ANALYSIS REVEALS WHIRLIN AS A DYNAMIC ORGANISER IN THE GROWING HAIR CELL STEREOCILIUM

Kikkawa Y1, Mburu P1, Morse S1, Kominami R2, Townsend S1, Brown S1

1 MRC, Harwell, United Kingdom, 2 Tokyo Metropolitan Institute of Medical Science (Rinshoken), Tokyo, Japan

Stereocilia on the surface of hair cells are vital for the process of auditory transduction. Stereocilia develop in bundles with a regular staircase pattern, whose actin core is organised such that the barbed ends of actin filaments are located at the stereocilia tips where there is a continuous cycle of renewal of actin filaments by addition of actin monomers. What little we know of the molecular processes that control actin polymerisation and stereocilia growth come from studies of mouse mutants with defects in stereocilia development, including the shaker2 (myosin XVa) and whirler mutants. The PDZ protein whirlin is known by virtue of the whirler mutation to be involved in the process of stereocilia organisation (Mburu et al, Nature Genetics 2003). We have investigated the expression of whirlin and myosin XVa in developing stereocilia in wild-type and whirler and shaker2 mutants. Whirlin localises to the actin-free zone at the tips of stereocilia. Expression of whirlin is dynamic during stereocilia growth demonstrating an ordered appearance and fade-out across the stereocilia rows and revealing a novel molecular gradation of process traversing the developing stereocilia bundle. Fade-out of whirlin in inner hair cells precedes that of outer hair cells consistent with the earlier maturation of inner hair cell stereocilia. In myosin XVa mutants in which stereocilia are shortened, whirlin is still expressed in the stereocilia tips but fade-out is accelerated. The data indicate that whirlin is a critical and dynamic organiser for proteins involved in stereocilia elongation and actin polymerisation.

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