Biomedical Engineering Reference
In-Depth Information
movements (
Wallingford et al., 2000
). Moreover, cells with abrogated
Wnt/PCP activity cannot undergo mediolateral cell intercalations with
neighboring normal cells in
Xenopus
(
Kinoshita et al., 2003
). Similarly,
in zebrafish, embryos with abrogated Wnt/PCP activity exhibit
defective cell intercalation behavior, which can be visualized by labeled
cells lateral to the shield, distributing as in a string along the AP axis as
gastrulation proceeds (
Heisenberg et al., 2000; Sepich et al., 2000
).
Whereas there is no obvious effect of altered Wnt/PCP activity on
collective migration of head mesendoderm cells in
Xenopus
, abrogation of
the Wnt/PCP pathway can lead to reduced migration of prechordal plate
progenitors in zebrafish (
Ulrich et al., 2005
). This is primarily due to reduc-
tion in coherence of the cells in
wnt11
mutants as Wnt11 is required for
E-cadherin-mediated cell cohesion (
Ulrich et al., 2005
). This suggests
that the Wnt/PCP pathway mediates cell cohesion underlying collective
migration of a large population of mesenchymal cells.
3.2. Neural tube defects in mice
Similar to zebrafish, identification of mouse mutants that exhibit severe neural
tube defects (NTD), reminiscent of craniorachischisis in humans, has uncov-
ered the core PCP genes
vangl2
and
celsr1
(
Curtin et al., 2003; Kibar et al.,
2001; Murdoch et al., 2001
). In addition, double mutants for
dvl1;dvl2
or
fzd3;fzd6
show the severe NTD phenotype (
Hamblet et al., 2002; Wang,
Guo, et al., 2006; Wang, Hamblet, et al., 2006
). Besides the core members
of the PCP pathway, mouse genetics has further identified new members
of the vertebrate PCP pathway. Despite the fact that
scribble (scrb)
is
implicated in regulating basolateral polarity in
Drosophila
(
Albertson & Doe,
2003
),
scrb
was identified from classical mouse mutants, exhibiting a severe
NTD (
Murdoch et al., 2003
). Further, mutants in the
ptk7
locus, encoding
a receptor tyrosine kinase, exhibit severe NTD and genetically interact
with
vangl2
(
Lu et al., 2004; Paudyal et al., 2010
).
Further analysis of the PCPmutant embryos at early-somite stages revealed
thatNTDarise primarily due to defectiveCEmovements in thenotochord and
neural plate (
Ybot-Gonzalez et al., 2007
). Indeed, CE is mediated by
mediolateral cell intercalations that contribute to extension of the axial tissue
(
Yamanaka et al., 2007; Yen et al., 2009
). However, it is still unclear
whether CE defects in mesenchymal notochord cells secondarily affect CE
in overlying neuroepithelial cells or defects
in the two layers occur
independently (
Table 4.1
).
