270
blocking mesoderm formation. Additionally, mutation or inhibition of wnt11 func-
tion in fish and frogs indicated that Wnt/PCP signaling was indeed required for
convergent extension behavior in vivo (Tada and Smith 2000 ; Heisenberg et al.
2000 ). Importantly, Wallingford et al. ( 2000 ) showed in detailed live imaging of
explants that Dvl activity was needed for bipolar cell shape changes and for stabiliz-
ing mediolaterally oriented bilateral protrusive activity of lamellopodia in converg-
ing and extending mesodermal cells. And similar regions of the protein were
required for controlling CE in Xenopus as for Drosophila PCP, namely the
C-terminal DEP domain (Wallingford et al. 2000 ). Analogous results were found
for zebrafish wnt11 and wnt5a mutants, which showed unstable monopolar protru-
sive activity in dorsally migrating cells (Kilian et al. 2003 ; Ulrich et al. 2003 ). Other
PCP proteins have also been shown to control cell intercalation by regulating
mediolateral lamellopodia in fish and frogs, including Frizzleds, Vangl2, and Prickle
(Djiane et al. 2000 ; Darken et al. 2002 ; Goto and Keller 2002 ; Jessen et al. 2002 ;
Wallingford et al. 2002 ; Veeman et al. 2003b; Takeuchi et al. 2003 ), as well an extra-
cellular modulator of Wnt, Glypican 4 (knypek, Topczewski et al. 2001 ).
More recent data from amniotes has shown that the regulation of cell shape and
the formation of mediolateral lamellopodia are conserved in mouse (Ybot-Gonzalez
et al. 2007 ; Yen et al. 2009 ; Williams et al. 2014 ) and chicken (Voiculescu et al.
2007 ). Additionally, mutations in core Wnt/PCP proteins in mice and humans
display axis elongation and neural tube defects, both of which depend on convergent
extension (Vangl1/2, Kibar et al. 2001 ; Murdoch et al. 2001 ; Montcouquiol et al.
2003 ; Kibar et al. 2007 ; Torban et al. 2008 ; Celsr1, Curtin et al. 2003 ; and Dvl1/2,
Wang et al. 2006 ). Also, noncore vertebrate Wnt/PCP regulators Ptk7 and Scrib are
also required for axis elongation and convergent extension, with Ptk7 likely directly
controlling bipolar protrusive activity (Montcouquiol et al. 2003 ; Lu et al. 2004 ;
Yen et al. 2009 ). The exact role of Ptk7 is unclear, although genetic experiments in
zebrafish have suggested a role in antagonizing Wnt/beta-catenin signaling to allow
Wnt/PCP signaling (Hayes et al. 2013 ). However, beta-catenin-activating roles
have also been described suggesting temporal or context-dependent roles.
In addition to controlling cell intercalation during convergent extension, Wnt/PCP
signaling is also implicated in cell intercalation prior to primitive streak formation. In
the chicken, local cell intercalation in the presumptive primitive streak region prior to
gastrulation is though to result from, and may facilitate the polonaise movements in
the epiblast. A number of Wnt/PCP components are expressed in the midline prior to
primitive streak formation and inhibition by electroporation of anti- PCP morpholino
oligos can inhibit streak morphogenesis (Voiculescu et al. 2007 ). Additionally, and
consistent with the role of the hypoblast in controlling polonaise movements, rotation
of the hypoblast can alter Wnt/PCP gene expression, possibly through Fgf8 signaling
(Voiculescu et al. 2007 ). Interestingly, it is likely that ingression itself can function
locally to organize polonaise-like movements and pull additional cells into the streak,
thus driving ingression in a feed-forward manner (Voiculescu et al. 2014 ).
The situation is less clear in mammals, as Wnt/PCP components have not been
widely implicated in primitive streak formation in the mouse. However, ingression at
the primitive streak in the mouse does require the down-regulation of Vangl2 protein,
D.W. Houston