Biomedical Engineering Reference
In-Depth Information
undergo mesoderm induction in the primitive streak. In contrast, in
mesd
mutants,
Cripto
is expressed properly. Mesoderm induction occurs when
b
-catenin directly induces the transcription of
Brachyury
and other targets.
Therefore,
-catenin
has two distinct effects during gastrulation: an early
effect on D-V to A-P axis rotation via
Cripto
and an unknown Wnt and
a later effect on mesoderm induction via
Brachyury
and other genes due
to
Wnt3
(
Morkel et al., 2003
). It is important to note that in addition to
mediating Wnt signaling,
b
-catenin also has an essential function in the
formation of the cadherins junction (
Nelson & Nusse, 2004
). Although
removal of
b
-catenin does not appear to alter intercellular adhesion,
presumably due to the compensatory substitution by plakoglobin
(
Huelsken et al., 2000; Lickert et al., 2002
),
b
it might interfere with
morphogenetic movements
-catenin-mediated dynamic
regulation of cadherins junction formation and may play some role in
PCP signaling.
that
require
b
2. PCP PATHWAY, A NONCANONICAL Wnt PATHWAY
Exposure to certain Wnts (such as Wnt5a) did not induce transforma-
tion of certain cultured mammalian cells or stabilization of
-catenin
(
Wong, Gavin, &McMahon, 1994
), which is a typical response to treatment
of Wnt1 or Wnt3a. Instead, a number of distinct pathways, including JNK
signaling, small GTPase Rho/Rac/Cdc42 signaling, and Ca
2
þ
signaling,
have been proposed as the downstream targets of these “noncanonical”
or Wnt5a class Wnts (
Veeman, Axelrod, & Moon, 2003; Wallingford &
Habas, 2005
). As these targets are also subjected to regulation by
numerous other signals, we do not have a definitive biochemical assay to
measure the activation in response to each noncanonical Wnt. Our
current understanding of the noncanonical Wnt pathway is based on
studies in other model organisms including
Drosophila
,
Xenopus
, and
zebrafish (
Goodrich, 2008; Wang & Nathans, 2007; Zallen, 2007
). The
noncanonical Wnt/PCP pathway shares two critical components with the
canonical Wnt pathway: the Fz receptor and a multifunctional
cytoplasmic protein Dishevelled (Dsh in flies, XDsh in frogs, and Dvl in
mice) (
Wallingford & Habas, 2005
). However, all the other members of
this pathway are distinct from those of the canonical Wnt pathway and
no Wnt ligand appears to be involved (
Chen et al., 2008; Povelones,
Howes, Fish, & Nusse, 2005
). The main function of this pathway is to
define PCP, the polarity of a cell within the plane of the epithelium,
b
