Biomedical Engineering Reference
In-Depth Information
role as a core PCP determinant and a component of theWnt pathway. These
observations led many to speculate that perhaps Wnts established PCP.
However, there is no evidence that Wnt ligands have a role in PCP in flies.
Depending on the receptor complex and intracellular environment
within the receiving cell, the Wnt signal is transduced down one of several
different pathways (
Cadigan & Liu, 2006
). If the ligand binds a Fz and a low-
density lipoprotein receptor, it activates the “canonical pathway” (
Wehrli
et al., 2000
). Canonical activity results in stabilization of
b
-catenin and the
formation of a
b
-catenin/Lef/Tcf transcriptional complex. If the Wnt inter-
acts with a Fz and Ror1/2, then a noncanonical/
b
-catenin-independent
cascade is activated (
Green, Inoue, & Sternberg, 2008; Mikels & Nusse,
2006; Oishi et al., 2003
). The noncanonical transduction cascade is still not
well understood, although, in some instances, it may involve activation of
Rho GTPases and Jnk (
Boutros, Paricio, Strutt, & Mlodzik, 1998; Habas,
Dawid, & He, 2003; Kohn & Moon, 2005; Oishi et al., 2003
). Ultimately,
activation of the noncanonical pathway results in polarization of the
cytoskeleton and PCP. The two pathways appear to antagonize each other
so that in one particular cell at one particular moment, only one pathway
maybeactive(
Green et al., 2008; Liao et al., 2006; Mikels & Nusse, 2006
).
Although it would be attractive to think that gradients of Wnt
proteins play a role in establishing PCP, there is little evidence that this is
the case (
Strutt, 2009
). In some instances, it appears that Wnts play permis-
sive roles in PCP while in others they are instructive (
Gao et al., 2011;
Goldstein, Takeshita, Mizumoto, & Sawa, 2006; Gong, Mo, & Fraser,
2004; Green et al., 2008; Heisenberg et al., 2000; Matsui et al., 2005;
Prasad & Clark, 2006; Schlesinger, Shelton, Maloof, Meneghini, &
Bowerman, 1999; Ulrich et al., 2003; Witze, Litman, Argast, Moon, &
Ahn, 2008
). How the activation of
the Wnt pathway affects planar
polarity is still not clear.
2.4. The primary cilium
The primary cilium is a small projection present on the apical side of most
cells, which consists of membrane surrounding a cytoskeletal structure
known as the axoneme. The axoneme is anchored within the basal bodies
that further act as anchoring or nucleation sites for other cytoskeletal
components and various cytosolic proteins as well as forming a part of the
centrioles during cell division (
Pan, Wang, & Snell, 2005
). In some tissues,
the cilia show planar-polarized localization within the apical membrane
