Biomedical Engineering Reference
In-Depth Information
Figure 11.2 Wnt signaling pathways. In the canonical Wnt/
b
-catenin pathway (right
panel), secreted Wnt proteins bind the Frizzled (Fz) and low-density lipoprotein
receptor-related proteins 5 and 6 (LRP) coreceptors to activate Disheveled (Dvl) leading
to the stabilization of
-catenin, which then enters into the nucleus, where it binds T cell
factor/the lymphoid enhancer factor (TCF/Lef) to transactivate target genes expression.
In the Wnt/PCP pathway (middle panel), Wnt proteins also bind Fz, which recruits Dvl.
On the other hand, Wnt proteins bind receptor tyrosine kinase orphan receptor (Ror) to
form a complex with Vangl, which recruits Prickle (PK). As a result, Vangl is phosphor-
ylated in a Wnt dose-dependent manner. It is proposed that PK and Dvl bind and
antagonize each other to generate asymmetrical protein localization, a critical regula-
tory event of PCP. Other receptor tyrosine kinases including PTK7 and Ryk are also
involved in PCP (left panel).
b
“noncanonical” pathways and that, in a particular cell, the specific
combination of receptors determines that one pathway dominates over
the other. While the term “noncanonical Wnt pathway” is being widely
used in the literature, its definition is quite loose (
Semenov, Habas,
Macdonald, & He, 2007
). Among of them, Wnt/calcium and Wnt/PCP
pathways have been studied more extensively (
Kohn & Moon, 2005;
Veeman, Axelrod, & Moon, 2003
). However, the
in vivo
function of
Wnt/Calcium pathway still awaits rigorous genetic tests in mammals.
While the
in vivo
evidence in mouse embryos has shown that Wnt sig-
naling is required in PCP pathway, the underlying mechanism by which
Wnt signaling regulates PCP remains largely unknown. The Frizzled family
proteins are assumed to mediate Wnt signaling due to their abilities to bind
