Inhibition of myosin II activity disrupts cochlear CE. (A)
Outgrowth of the sensory epithelium was assayed by cutting the intact cochlear
duct at its midpoint and then maintaining the basal piece in vitro. Over the
subsequent 72-96 hours the sensory epithelium extended outwards from the cut
end of the explant. (B) Control explant established as described in A.
The site of the initial cut is marked in white. The sensory epithelium (hair
cells marked in red) extends from the initial cut site. (C) Explant
established as in B, but treated with 10 μM of the myosin II inhibitor
blebbistatin beginning at E14. The sensory epithelium is noticeably shorter
and wider. (D) An explant established as in B, but treated with 10
μM of the ROCK inhibitor Y27632. The phenotype of the sensory epithelium is
similar to that in C. (E,F) Images of the sensory epithelium
from control (E) and 10 μM blebbistatin-treated (F) explants labeled with
anti-myosin 6 (red) and phalloidin (green). Additional inner pillar cells (PC)
are present in blebbistatin-treated explants. Patterning in the IHCs and OHCs
is also disrupted. Abbreviations as in Fig.
2. (G) Treatment with either blebbistatin or Y27632 results
in a significant and dose-dependent decrease in extension of the sensory
epithelium. By contrast, the skeletal muscle myosin inhibitor BTS did not
affect extension. (H) Treatment with 10 μM blebbistatin leads to a
significant increase in the width of the sensory epithelium. However, the
width of the sensory epithelium was not significantly increased in explants
treated with 10 μM Y27632. (I) Blebbistatin treatment leads to
changes in cell shape that are consistent with changes in
Myh10DN mutants. (J,K) Surface (upper panel)
and cross-section (lower panel) views of control (J) and blebbistatin-treated
(K) explants labeled with an antibody specific for the tight junction protein
ZO1 (green). Tight junctions are present in explants from both conditions and
are restricted to the lumenal surfaces. Scale bars: 50 μm in B (same
magnification in C,D); 20 μm in E (same magnification in F,I,J).
*P<0.005, **P<0.001,
***P<0.01.