Biomedical Engineering Reference
In-Depth Information
3.4. Localization of core PCP proteins and CE behavior
In the authentic view of PCP in the
Drosophila
wing, the core PCP proteins
are asymmetrically localized to establish planar polarization such that the com-
plexes Fz-Dsh and Vang-Pk are localized on distal and proximal sides, respec-
tively, through the mutually antagonistic interactions (
Bastock et al., 2003
;
Jenny et al., 2005
;
Tree et al., 2002
). The long-range cell-nonautonomous
effects of PCP are mediated by the Fmi, Fz, and Vang through different
mechanisms in
Drosophila
(
Lawrence et al., 2008b
). During zebrafish
gastrulation, similarly, anteriorly localized Pk and posteriorly biased Dsh are
observed in both somite and notochord progenitor cells undergoing CE,
and the asymmetric localization of these proteins is disrupted in core PCP
mutants (
Yin et al., 2008
). Consistent with the idea that mutually antagonistic
activities between Pk and Dsh can establish such asymmetric localization of
the two proteins, overexpression of Pk leads to downregulation of Dsh in
the zebrafish gastrula (
Carreira-Barbosa et al., 2003
). Interestingly, the ante-
riorly biased Pk localization is microtubules (MT) dependent (
Sepich et al.,
2011
), and this is indeed supported by the notion that MT polarity is upstream
of the establishment of PCP in the
Drosophila
wing (
Shimada et al., 2006
). De-
spite the asymmetric localization using
Drosophila
GFP-Pk and
Xenoups
Dvl2-GFP (
Yin et al., 2008
), neither zebrafish GFP-Pk1b nor Dvl2-GFP ex-
hibits such asymmetric localization in notochord progenitors (M. Tada,
unpublished results). To exclude the possibility of ectopic localization primar-
ily due to gain-of-function effects, this issue needs to be clarified by using an-
tibodies to detect endogenous localization or by knocking-in GFP-tagged
constructs into the endogenous locus based on BAC manipulation.
Another interesting feature of lateral mesoderm progenitors undergoing
CE is that the positioning of microtubules organizing centre (MTOC) is
posteromedially or posterolaterally biased, and its localization is randomized
in embryos with compromised PCP function (
Sepich et al., 2011
). This
MTOC localization is different to the authentic view in which MTOC is
localized toward the direction of their migration in cultured cells, despite
the fact that noncanonical Wnt/PCP signal regulates MT polarity in
cultured cells (
Schlessinger et al., 2007
). In relation to the ability of Wnt/
PCP signal to modulate MT polarity, there is increasing evidence that
ciliary-associated proteins can regulate CE by interacting with the
Wnt/PCP pathway including Inv, Bbs4, and Bbs8 (
Gerdes et al., 2007;
May-Simera et al., 2010; Ross et al., 2005; Simons et al., 2005
).
