Biomedical Engineering Reference
In-Depth Information
phenotypes are more severe than those of the
Wnt5a
/
mutant, suggesting
that Ror1/2 may also transduce signals of other Wnt proteins. However, in
the limb, distal digits of forelimbs of the
Ror1
/
and
Ror2
/
double
mutant embryo still form. This phenotype is much less severe than that of
the
Wnt5a
/
mutant, suggesting that there are some other receptors
mediating the Wnt5a signal (
Ho et al., 2012
).
Ryk, another single transmembrane receptor tyrosine kinase with
unfunctional kinase domain (
Halford & Stacker, 2001
), binds to Disheveled.
It potentiates Wnt1 and Wnt3a-dependent gene expression and is required
for axon guidance and Wnt3a-induced neurite outgrowth (
Lu, Yamamoto,
Ortega, & Baltimore, 2004
). Several groups showed that Ryk is also re-
quired for Wnt5a-mediated axon guidance in both
Drosophila
and mammals
(
Li, Hutchins, & Kalil, 2009; Yoshikawa, McKinnon, Kokel, & Thomas,
2003
). In addition, Wnt5b has been identified to provide an instructive
cue to regulate zebrafish gastrulation movements through Ryk (
Lin,
Baye, Westfall, & Slusarski, 2010
). Therefore, Ryk appears to mediate
both
b
-catenin-dependent and
b
-catenin-independent pathways. Very
recently, Stacker's group demonstrated that Ryk is involved in PCP
pathway in vertebrate. They found Ryk genetically interacts with Wnt11
during CE movement in zebrafish. In mouse,
Ryk
/
mutant exhibited
sensory hair cell orientation defects in inner ear cochlea and Ryk
genetically interacts with Vangl2 (
Macheda et al., 2012
).
The tyrosine kinase receptor Ptk7 with a defective kinase domain was
originally identified as a PCP protein because its mutation disrupts neural
tube closure and inner ear hair cell polarity in mouse, and it genetically
interacts with Vangl2 (
Lu et al., 2004
). In
Xenopus
, Ptk7 was shown to be
required for Frizzled7-mediated Disheveled localization and regulate neural
crest migration (
Shnitsar & Borchers, 2008
). While the Ptk7 was strongly
implicated in Wnt/PCP pathway, its role in canonical Wnt signaling seems
to be controversial.
Puppo et al. (2011)
reported Ptk7 positively regulates
Wnt/
b
-catenin signaling upstream from GSK3. However, Peradziryi
et al. showed Ptk7/Otk inhibits canonical Wnt signaling. They also showed
Ptk7 coimmunoprecipitates with Wnt3a and Wnt8, but not Wnt5a and
Wnt11 (
Peradziryi et al., 2011
). Nevertheless, whether Ptk7, which does
not contain any known Wnt proteins binding domain, is a true Wnt recep-
tor remains to be determined.
Despite innumerable successful gene discoveries in the Wnt/
b
-catenin
signaling pathway, which is mainly based on the convenient TCF/LEF
luciferase assay (Topflash), advances in finding regulatory components of
