Biomedical Engineering Reference
In-Depth Information
to visualize, the organ of Corti in the cochlear duct represents one of the few
tissues in which asymmetric localization of PCP proteins has been
demonstrated. Prior to the migration of the kinocilium, Vangl2 becomes
localized to cell-cell junctions between the proximal regions of developing
hair cells and the distal regions of developing supporting cells
(
Montcouquiol et al., 2006
). While it has not been possible to determine
whether Vangl2 is present in hair cells, support cells, or both, the
predominant expression at these boundaries seems consistent with results
from
Drosophila
. Similarly, consistent observations were made for Dvl1, and
Dvl2, both of which appeared to localize in the distal regions of
developing hair cells (
Wang, Hamblet, et al., 2006; Wang et al., 2005
).
While the results described above are consistent with a conservation of
PCP signaling mechanisms between fly wing and vertebrate inner ear, sev-
eral recent studies have suggested either significant deviations or the
existence of more complex patterns of polarization within the inner ear.
As discussed, codeletion of
Fz3
and
Fz6
leads to bundle orientation defects,
and by analogy with
Drosophila
, Fz3 and Fz6 would be expected to localize
on the same side of the cell as Dvl. However, localization of Fz3 and Fz6 in
the developing cochlea indicated colocalization with Vangl2 on the medial
side of developing hair cells (
Wang, Guo, et al., 2006
). This result was some-
what surprising and was made more so by the observation that in developing
vestibular epithelia, Fz3 and Fz6 localized to the distal side of hair cells.
Subsequently, a study examining localization of Prickle2 (Pk2), a vertebrate
homolog of pk, in the vestibular system, took advantage of the reversal zone
that exists within the utricle to determine whether localization of Pk2
changes with orientation (
Deans et al., 2007
). Results indicated an asymmet-
ric localization of Pk2 to one side of each hair cell and supporting cell,
but this asymmetry was unchanged on either side of the reversal zone
even though hair cell bundle orientation rotated by 180
. Finally,
immunolocalization for Vangl2 through the reversal zone of the chicken
utricle indicated no obvious switch in subcellular distribution (
Warchol &
Montcouquiol, 2010
).
These results have several intriguing implications. First, the asymmetric
distribution of multiple core PCP molecules is consistent with strong
polarization of both auditory and vestibular epithelia, as well as a general
conservation of the PCP signaling mechanism. But, the observation that
asymmetric distribution does not parallel stereociliary bundle orientation
suggests that bundle orientation may not be determined directly through
cellular polarization. Rather, the underlying polarity of the epithelium
