Planar Cell Polarity in Coordinated and Directed Movements - Current Topics in Developmental Biology - page 82

(lamellipodia in Xenopus ; both lamellipodia and blebs in zebrafish) toward
the direction of their migration ( Diz-Munozetal.,2010;Monteroetal.,
2003; Weber et al., 2012 ). Cells behind the leading edge migrate in a
coordinated manner with no neighbor exchanges involved. Migrating
cells utilize the overlying ectoderm as a substrate for migration (the
blastocoel roof in Xenopus ; the epiblast in zebrafish) ( Ulrich et al., 2003;
Winklbauer, 1990 ).
3. PLANAR CELL POLARITY SIGNALING IN VERTEBRATES
3.1. Identification of the vertebrate PCP pathway during
gastrulation
Despite the fascinated feature of coordinated and polarized cell behaviors
underlying CE, there was no clue as to what genetic pathway(s) mediate this
process until the end of the twentieth century. Identification of zebrafish
mutants, which exhibit a shorter body axis, and candidate approaches, using
dominant-negative constructs in Xenopus to test a plausible pathway that
inhibits CE movements but not mesoderm specification, has revealed that
the PCP pathway is key to mediating CE ( Heisenberg et al., 2000; Tada
& Smith, 2000; Topczewski et al., 2001; Wallingford et al., 2000 ).
Within a decade, it has been demonstrated that core members of the
Drosophila PCP pathway all play roles in regulating CE in zebrafish and
Xenopus except that vertebrates utilize Wnt ligands. Hereafter, this refers
to as the Wnt/PCP pathway, which includes the ligands Wnt11 and
Wnt5, the receptors Frizzled7 (Fzd7) and Fzd2, the membrane cofactor
Glypican4 (Gpc4), the transmembrane protein Vangl2 and Flamingo
(Fmi)/Celsr1/2, and the intracellular proteins Disheveled (Dsh/Dvl),
Prickle (Pk), and Diego (Dgo)/Diversin/Inversin (Inv) ( Carreira-Barbosa
et al., 2003, 2009; Darken et al., 2002; Djiane et al. & Shi, 2000;
Formstone & Mason, 2005; Goto & Keller, 2002; Heisenberg et al., 2000;
Jessen et al., 2002; Kilian et al., 2003; Ohkawara et al., 2003; Park &
Moon, 2002; Rauch et al., 1997; Schwarz-Romond et al., 2002; Simons
et al., 2005; Sokol, 1996; Tada & Smith, 2000; Takeuchi et al., 2003;
Topczewski et al., 2001; Veeman et al., 2003; Wallingford et al., 2000 ).
The Wnt/PCP pathway is required for both the orientation and
polarization of cells undergoing CE ( Sepich et al., 2000; Topczewski
et al., 2001; Wallingford et al., 2000 ). Likewise, elevated PCP activity
leads to disrupted elongation/orientation of cells, thereby inhibiting CE