Airway Surface Liquid and Respiratory Mucus - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 779

12.6.3 Ciliogenesis

The respiratory epithelium is often restored after biological, chemical, or physical
damage. Ciliogenesis is complete within 14 days in vivo. Motility and morphology
of cilia during ciliogenesis can be studied in human respiratory epithelial cells in
floating culture. On day 7, cells exhibit numerous microvilli, but no cilia. On day 8,
cilium length was approximately 2

m.
On day 8 of culture (rarely before), cells with numerous short moving cilia can
be observed (mean ciliary beat frequency 17.8

m, whereas on days 12 to 14, it was 5 to 7

± 2.5 Hz) [ 1589 ]. Mean ciliary beat

frequency that begins on day 8 of culture (17.8 ± 2.5 Hz) reaches its highest value

on day 10 (19.6 2.5 Hz on day 14).

Ciliary beat amplitude detected on day 8 rises on day 9 and then continues.
Immature short cilia have a rigid beat pattern. As cilia lenghten, flexible cilium
forward and backward motions gradually synchronize. Ciliary beat direction is
random on day 8, but beat coordination for a given cell and for cell population
is established after days 12 and 14, respectively.
Therefore, ciliogenesis is complete within 14 days. At early stage of ciliogenesis,
ciliary beat frequency and amplitude is high and low, respectively. High ciliary beat
frequency does not reflect activity of mature cilia.
During differentiation of tracheal epithelial cells, hundreds of centrioles migrate
to the apical surface of the cell, dock with the membrane to form basal bodies, and
act as templates for the outgrowth of the outer microtubule doublets of the ciliary
axoneme [ 1590 ].
Centrioles involved in ciliogenesis are generated by 2 processes [ 1591 ]. Early
stages of formation of both primary cilia and ciliated border are similar. Rudimen-
tary (primary) cilia arise from centrioles in differentiating pulmonary cells of all
types throughout the fetal period. Annular procentrioles lengthen into cylinders to
give rise to daughter centrioles. When mature, newly formed centrioles align in rows
beneath the apical plasma membrane, where each centriole produces satellites from
its sides, a root from its base, and a cilium from its apex. In developing cilia of the
ciliated border, outer ciliary tubules rapidly reach the tips of the elongating shafts,
and a central pair of tubules is formed, whereas in primary cilia, tubule development
lags behind shaft elongation and only outer ciliary tubules appear.
Hedgehog signaling is mediated by protein Ser/Thr kinase Fused for assembly of
the central microtubule pair of motile cilia that regulates ciliary motility [ 1590 ]. 29
Fused is strongly expressed in the respiratory epithelium. Fused interacts with
kinesin family member KIF27 (but not KIF7) to link Fused to structural components
of the central pair apparatus. Expression of Fused and KIF27 is upregulated during
tracheal epithelial cell differentiation.

± 3.9 Hz) to decay afterward (17.4 ±

29 Mice lacking functional Fused have defects or loss in central pairs, hence impaired cilium motion
and mucociliary transport (reduced forward power stroke amplitude, uncoordinated ciliary beating,
etc.).