Biomedical Engineering Reference
In-Depth Information
interesting to investigate whether Wnt-regulated Vangl2 phosphorylation also
regulates endocytosis and contributes to PCP establishment (
Gao et al., 2011
).
An interesting pattern of asymmetrical localization of PCP components
is that Vangl and Prickle are always localized opposite to the direction of
increasing Wnt dosages. But Disheveled, probably Frizzled, is often local-
ized to the plasma membrane along the direction of increasing Wnt dosages.
For instance, in the early developing limb, there is a distal to proximal Wnt5a
gradient (
Yamaguchi et al., 1999
) and Vangl2 is localized to the proximal
side of the plasma membrane (
Gao et al., 2011
). In the mouse node, Vangl1,
Vangl2, and Prickle2 are preferentially localized on the anterior side of cell
membrane (
Antic et al., 2010; Song et al., 2010
) opposite to bothWnt3a and
Wnt5a gradient from posterior tail bud. But Disheveled proteins are
localized to the posterior edge of node cells (
Hashimoto et al., 2010
).
Similarly, in the zebrafish gastrulae, PK and Dvl are enriched near
anterior and posterior cell membranes, respectively (
Yin, Kiskowski,
Pouille, Farge, & Solnica-Krezel, 2008
). In the basal layer of mouse back
skins, Vangl2 is also asymmetrically accumulated on the anterior side of
cell membrane, although the identity of Wnt gradient is unknown in this
context (
Devenport & Fuchs, 2008; Devenport, Oristian, Heller, &
Fuchs, 2011
). In the mouse eye, Vangl2 is predominantly localized to the
anterior pole side of lens cells, but positions of other PCP proteins
(Frizzled6, Disheveled2/3, and Prickle1) appear quite complicated
(
Sugiyama et al., 2010
). Interestingly, although Wnt protein expression is
dynamic in the developing lens, their expression is predominantly
restricted to the cells at the lens equator at later embryonic states (
Ang,
Stump, Lovicu, & McAvoy, 2004
), suggesting there might have been a
Wnt gradient from equator to anterior pole. Therefore, it will be
interesting to identify the mechanism whereby the direction of Wnt
gradient determines the pattern of PCP protein localization, a critical
aspect of Wnt regulation of PCP as global cue.
4. CONCLUSION
In the past, the efforts focused on identifying new PCP components
and regulatory mechanisms of PCP have been most productive in
Drosoph-
ila.
The functions and the underlying mechanisms of PCP in different organs
and tissues of vertebrates are also being revealed. However, a critical ques-
tion that remains unanswered is how a large group of cells orient in the same
