Biomedical Engineering Reference
In-Depth Information
With these caveats in mind, the auditory system still has considerable
potential as a model system for studying PCP. As demonstrated by the
Sienknecht, Anderson, Parodi, Fantetti, and Fekete (2011)
study, the exis-
tence of broad fields of hair cells in both avian and mammalian inner ears
provides a unique opportunity to test hypotheses related to autonomous ver-
sus nonautonomous signaling by PCP proteins as well as to examine the pos-
sible roles of Wnt morphogens in the generation of polarity. However,
while effects on bundle orientation cannot be ignored, it will be equally
important to determine changes in asymmetric protein localization and to
consider the degree of correlation between the two. Further, as the ability
to generate tissue- and cell-specific mutations increases, it will be extremely
enlightening to determine the effects of bundle rotations and other PCP
defects on the specific functions of the inner ear. The rotation of even a small
number of bundles has been shown to lead to specific defects in the percep-
tion of some frequencies (
Yoshida & Liberman, 1999
), but the effects of sim-
ilar rotations on vestibular function or other aspects of auditory perception
remain to be determined.
Finally, the additional role of PCP signaling in the extension and
patterning of the cochlear duct provides both a new and intriguing model
system for the study of PCP signaling and, unfortunately, a confounding
factor in the analysis of PCP-mediated effects. Recent work has demon-
strated that the alignment of auditory hair cells is dependent on the success-
ful outgrowth of the duct (
Wang et al., 2005; Yamamoto, Okano, Ma,
Adelstein, & Kelley, 2009
), suggesting that PCP signaling plays a key
regulatory role in the morphogenetic movements required to generate
these ordered rows. Further studies should be able to take advantage of
this developmental process to better understand how cells become
precisely aligned. However, outgrowth defects that result in misaligned
hair cells, often manifesting in the formation of fourth or fifth rows of
outer hair cells, have the potential to lead to bundle misorientation as a
secondary effect. As discussed, hair cells located in the third row
demonstrate heightened sensitivity to PCP defects. Therefore, it seems
possible that hair cells located in ectopic fourth or fifth rows might
demonstrate disruptions in bundle alignment, not because of a direct role
of a particular gene in bundle orientation but because of a role of that
gene in cellular patterning. As is the case for many future studies, the
ability to target genetic deletions to individual cell types at specific
development time points will be required in order to be able to address
these possibilities.
