Biomedical Engineering Reference
In-Depth Information
Oristian, Heller, &Fuchs, 2011; Guo, Hawkins, &Nathans, 2004
). These data
provide strong evidence that Celsr1 is involved in classical PCP together with
Fzd3 and 6, Dvl1 and 2, and Vangl2.
3. CELSR2 AND 3 IN CILIOGENESIS
Cilia are appendages that extend from the cell surface to the extracel-
lular environment. Based on their structure and motility, cilia are classified
into three types: motile, primary, and nodal cilia (
Davenport & Yoder,
2005
). Motile cilia garnish the apical surface of epithelial cell lining airways,
reproductive tracts, and cerebral ventricles. They have a central pair of mi-
crotubules surrounded by nine doublet of microtubules, an organization
known as 9
2, and are anchored to a basal body in the apical cortex. Motile
cilia form tufts and their concerted beats generate directional flow at the sur-
face of epithelial sheets. In the airways, they are crucial for clearing mucus
and debris, and in genital tracts, they assist in the transit of sperm and eggs
(
Salathe, 2007; Voronina et al., 2009
). In the mouse brain at late embryonic
stage and during the first postnatal week, neuroepithelial cells that line the
cerebral ventricles differentiate into a monolayer of ependymal cells. At
birth, ependymal cells are not multiciliated yet (
Fig. 7.3
). Motile cilia
develop progressively and reach their mature shape by the end of brain
maturation (
Fig. 7.3B
). The basal body of each cilium has a lateral
extension called “basal foot” that can be detected by transmission
electron microscopy. Basal feet point in the effective beat direction and
are used as a hallmark of cilia polarity (
Gibbons, 1961; Hagiwara,
Ohwada, Aoki, Suzuki, & Takata, 2008; Wallingford, 2010
). To generate
an efficient directional flow, cilia coordinate their beats within the same
cell (each cell has dozens of motile cilia) and in all cells in the epithelial
sheet. Thus, basal feet are aligned in the same orientation with respect to
the tissue polarity axis, a process referred to as “rotational polarity”
(
Mirzadeh, Han, Soriano-Navarro, Garcia-Verdugo, & Alvarez-Buylla,
2010
). Elegant studies in
Xenopus
ciliated epidermal explants isolated at
different developmental stages showed that motile cilia acquire their
rotational polarity in two steps. Early in development, genetic cues
specify a rough planar axis that allows cells to produce a directional flow,
thereby inducing a positive feedback loop that tunes basal feet polarity
(
Mitchell, Jacobs, Li, Chien, & Kintner, 2007
). In mice,
Celsr1
-
3
are
expressed in the developing ependymal layer. Mutation of
Celsr2
and
Celsr3
impairs ependymal ciliogenesis (
Tissir et al., 2010
). Although
differentiation of ependymal cells occurs normally, their motile cilia never
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