Biomedical Engineering Reference
In-Depth Information
May-Simera et al., 2009
). Potentially correct basal body/centrosome
positioning could be required for subsequent regulation of cytoskeletal
architecture.
Therefore, at this point, it seems unreasonable to try to definitively place
cilia-related signaling either upstream, downstream, or in parallel with PCP.
One could easily envisage a possible feedback loop where cilia-related sig-
naling mediates cytoskeletal architecture/function which then plays a role in
PCP signaling, which, in turn, regulates cilia position and function. Another
key issue to be considered here is whether all of the defects observed in
“ciliopathies” are actually a result of disruption in cilia function. Many of
the ciliopathy proteins are now being reported to be expressed in other
locations within the cell, suggesting that they could be mediating other
aspects of cellular biology and development.
6. LOOKING FORWARD: PCP SIGNALING IN THE INNER
EAR, WHERE DO WE GO FROM HERE?
As discussed, the very obvious uniform alignment of hair cell
stereociliary bundles and the direct link of this alignment with inner ear
function have made the inner ear one of the best model systems for studying
PCP in vertebrates. Bundle orientation has demonstrated a high degree of
sensitivity to perturbations in PCP signaling, in particular, in terms of ge-
netic interactions between key PCP molecules, such as Vangl2, and other
candidates that might not be sufficient to produce obvious results in simple
deletion models. Further, the very clear morphological manifestation of
PCP defects in terms of bundle rotation allows for straightforward quanti-
fication of orientation defects which can be used to confirm and compare
effects of different mutations. However, more recent studies have yielded
results which suggest that our understanding of polarization within the
auditory system is far more limited than once thought. The fact that asym-
metric localization of core PCP proteins does not directly correlate with
bundle orientation suggests that different types of polarization may occur
at multiple time points during the development of a given auditory epithe-
lium. Moreover, if asymmetric localization of core PCP proteins is a hall-
mark of PCP, then the observation that bundle orientation is not dictated
by this asymmetry suggests the possibility that bundle rotation should not
be considered as a readout of polarization. Needless to say, this would have
a significant impact on our understanding of how PCP functions within the
auditory system and on our ability to analyze PCP defects.
