Planar Cell Polarity in Coordinated and Directed Movements - Current Topics in Developmental Biology - page 97

5.2. CE and cell - cell adhesion
One unique feature of the ability of the Wnt/PCP pathway to modulate
cell-cell adhesion is mediated through the family of atypical Cadherin,
which does not utilize the module of Catenin complex linking with actin
cytoskeleton. Several lines of evidence support the notion that Fmi/Celsr
regulates cell cohesion/adhesion underlying CE behaviors. First, ectopic ex-
pression of celsr2 increases cell-cell contact persistency in cells of the
zebrafish blastula and colocalizes with Wnt11-Fzd7 at cell-cell contact
( Witzel et al., 2006 ). Second, dissociated cells with decreased endogenous
Celsr activity from zebrafish blastula embryos are segregated out of wild-
type cells in hanging drop assays ( Carreira-Barbosa et al., 2009 ). This is con-
sistent with the observation that, when celsr2 is overexpressed, individually
floating S2 cells become cohesive, making a cluster of the cells ( Shima et al.,
2004 ). However, loss of function of celsr1a/1b/2 leads to a defective epiboly
phenotype, which arises prior to CE taking place, making it difficult to
analyze CE cell behavior properly ( Carreira-Barbosa et al., 2009 ). Rather
than the stereotypic CE phenotype in zebrafish, embryos with abrogated
Celsr activity exhibit the epiboly phenotype, reminiscent of hypomorphic
alleles of e-cadherin mutants ( Kane et al., 2005 ). This raises the possibility that
Celsr modulates cell adhesion/cohesion through functional interaction with
E-cadherin either directly or indirectly.
The other atypical Cadherin mediating CE is paraxial protocadherin
(Papc). papc is identified as a transcriptional target for the Wnt5/Ror2/
JNK pathway in Xenopus ( Schambony & Wedlich, 2007 ) and has been
shown to be required for CE in Xenopus ( Medina et al., 2004; Unterseher
et al., 2004; Wang et al., 2008 ). One possible mechanism by which Papc
modulates cell adhesion is to act through classical Cadherins ( Chen &
Gumbiner, 2006 ). In support of this view, a ventrodorsal gradient of
BMP signal mediates convergence movement by modulating a
dorsoventral gradient of N-cadherin activity in zebrafish ( von der Hardt
et al., 2007 ). However, there is no direct evidence for Papc to act
downstream of BMP signal in Xenopus .
5.3. Cell - substrate adhesion and integration into apicobasal
polarity
The ability of Wnt/PCP signal tomodulate cell-substrate adhesion is also fun-
damental to the regulation of CE. A positive feedback loop, in which Wnt11
regulates Fibronectin assembly ( Dzamba et al., 2009 ) and Fibronectin-Integrin