Biomedical Engineering Reference
In-Depth Information
time, microvilli located adjacent to this cilium also begin to elongate to give
rise to individual stereocilia. Specifically in mechanosensory hair cells, this
cilium is referred to as the kinocilium. Importantly, the direction of the mi-
gration of the cilium/kinocilium is thought to determine the eventual ori-
entation of the stereociliary bundle. While the initial direction of this
migration is nonrandom and is biased toward the final orientation of the ma-
ture bundle, deviations of as much as 35
from the final orientation are ob-
served (
Cotanche &Corwin, 1991; Dabdoub et al., 2003; Denman-Johnson
& Forge, 1999
). Once the kinocilium reaches the lateral edge of the lumenal
surface, deviations are corrected during a period of refinement as developing
bundles gradually reorient to ultimately achieve uniform orientation
(
Fig. 5.2
). In the mouse cochlea, stereociliary bundle development and
orientation occur along two gradients, a predominantly basal-to-apical
gradient that begins in the mid-basal of the duct and a medial-to-lateral
gradient that begins in the inner hair cells and extends toward the third
row of outer hair cells. Final uniform orientation of all hair cells is not
achieved in the mouse until approximately P10 (
Dabdoub et al., 2003
).
Interestingly, while all stereociliary bundles are arranged in a staircase
pattern, the arrangement of the individual stereocilia varies based on loca-
tion. In the vestibular epithelia, bundles are generally round with the
kinocilia located at one edge. In contrast, in the cochlea, the morphology
of the bundle is modified such that bundles on inner hair cells are in the shape
of an arc, while bundles on outer hair cells appear more like a “W” although
with a very shallow central indentation. In both cases, the kinocilium is
located at the vertex of the structure. The functional significance of these
modifications in morphology is unclear but has been suggested to be linked
to the overall structure of the organ of Corti.
While the number of studies on the development of bundle orientation
in the vestibular system is more limited by comparison with the cochlea, the
overall progression seems similar although apparently less coordinated
(
Denman-Johnson & Forge, 1999
). Developing hair bundles can first be
identified around E12.5, approximately 48-72 h prior to the formation of
hair cells in the cochlear duct. The single true cilium (also referred to as a
kinocilium) begins to elongate and then moves in a nonrandom manner to-
ward one edge of the lumenal surface. As is the case in the cochlea, there is a
period of refinement that leads to more uniform orientations over time.
However, the overall process of polarization is more difficult to assay in
the vestibular epithelia because hair cells are not generated in a discrete gra-
dient as they are in the cochlea. Instead, hair cells seem to arise at random
