Biomedical Engineering Reference
In-Depth Information
CHAPTER FIVE
Planar Cell Polarity in the Inner Ear
Helen May-Simera, Matthew W. Kelley
1
Laboratory of Cochlear Development, NIDCD, NIH, Bethesda, Maryland, USA
1
Corresponding author: e-mail address: kelleymt@nidcd.nih.gov
Contents
1.
Introduction to the Inner Ear
112
2. Development of the Inner Ear
113
2.1 Extension of cochlea duct
115
2.2 Development and orientation of mechanosensory hair cell
stereociliary bundles
115
3. Molecular Mechanism of Planar Cell Polarity
118
3.1 Core PCP molecules
119
3.2 Effects of Wnt ligands
121
3.3 Asymmetric protein localization
122
3.4 Novel coreceptors
124
3.5 Cytoplasmic mediators
124
3.6 Downstream targets
125
3.7 The fat/dachsous pathway
127
4. Upstream Regulators of PCP
128
5. Cilia and Their Role in PCP
129
6. Looking Forward: PCP Signaling in the Inner Ear, Where Do We Go from Here?
133
References
135
Abstract
The inner ears of vertebrates represent one of the most striking examples of planar cell
polarity (PCP). Populations of directionally sensitive mechanosensory hair cells develop
actin-based stereociliary bundles that are uniformly oriented. Analysis of perturbations
in bundle polarity in mice with mutations in Vangl2 formed the basis for the initial dem-
onstration of conservation of the PCP signaling pathway in vertebrates. Subsequent
studies have demonstrated roles for other
PCP genes, such as Frizzled, Disheveled,
and Celsr, and for identifying novel PCP molecules such as Scribble and Ptk7. In addition,
the demonstration of hearing deficits in humans with mutations in cilia genes com-
bined with analysis of PCP defects in mice with ciliary deletion has implicated the cilia
as an important modulator of hair cell polarization. Finally, the presence of shortened
cochleae in many PCP mouse mutants has revealed an additional role for the PCP path-
way in the development of the auditory system.
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