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Fig. 6. Generation of stereociliary bundle orientation. (A,B) Side and lumenal
views of a hair cell illustrating the morphology of the mechanosensitive
stereociliary bundle. The stereocilia (green) are arranged in a staircase
pattern with a single microtubule-based kinocilium (red) located at one edge.
(C) Each circle illustrates the lumenal surface of a developing hair cell at
different time points. (C1) Prior to bundle formation, all developing hair
cells have a single cilium (red) that will develop as the kinocilium. (C2) As
development proceeds, the cilium moves from the center of the lumenal surface
towards the periphery (arrow). Most cilia move to a position that approximates
their final orientation. (C3) Next, the developing stereociliary bundle
(kinocilium in red and stereocilia in green) moves along the peripheral edge
of the cell (arrows) to attain its final orientation. (C4) Progressive
refinements ultimately result in the development of appropriate orientation.
(D) Hypothetical expression patterns for molecules that regulate bundle
orientation. (D1) Vangl2 (blue), Celsr1 (yellow) and Scrb1 (purple) are
thought to be expressed initially throughout hair cells. (D2) Prior to the
centrifugal movement of the cilium, Vangl2 is localized to the side of the
developing cell opposite the site of stereociliary bundle formation (the
proximal side) and Celsr1 is localized to both the proximal and distal sides
of the cell. (D3,D4) Wnt (dark shading) is thought to be distributed in a
gradient around the developing hair cell. Following centrifugal movement,
outer hair cells reorient their bundles towards the point of lowest Wnt
concentration. (E) Effects of different mutations on bundle orientation.
Mutations in Vangl2 (E2) result in a defect in the direction of
centrifugal movement. Similar effects are assumed for Scrb1 (E3) or
Celsr1 (E4) mutants. (F) Disruption of the Wnt gradient, either an
excess of Wnt (F2) or a deficiency (F3), results in inhibition of the bundle
reorientation.
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