Biomedical Engineering Reference
In-Depth Information
2. Wnt AND PLANAR CELL POLARITY
PCP was first discovered in the insects
Oncopeltus fasciatus
(
Lawrence &
Shelton, 1975
) and then extensively studied in
Drosophila melanogaster
,in
which a group of core PCP genes were identified (
McNeill, 2010; Seifert
& Mlodzik, 2007; Tree, Ma, & Axelrod, 2002; Vladar, Antic, & Axelrod,
2009
). Disruption of these core PCP proteins results in misorientation of
the bristles in the
Drosophila
wing and disarrangement of the ommatidia
in the
Drosophila
compound eye. In vertebrate embryos, such as frog
(
Xenopus laevis
) and zebrafish (
Danio rerio
), the same group of PCP
proteins regulates convergent extension (CE), a process coordinating
extension of the anterior-posterior (A-P) body axis while the
mediolateral (ML) axis was narrowed. The zebrafish PCP mutants failed
to extend their A-P axis properly leading to a shortened and broadened
body axis (
Gray, Roszko, & Solnica-Krezel, 2011; Wang & Nathans,
2007
). Using CE as a functional PCP readout in vertebrate, frog and
zebrafish have become popular model organisms to test genes regulating
PCP. In mammals, PCP regulates a diverse array of essential
developmental processes, ranging from neural tube closure to determining
left-right (L-R) asymmetry, indicating its fundamental roles in the
development of vertebrates (
Gray et al., 2011
). Not surprisingly, more and
more PCP mutations have been identified in various human diseases in
recent years (
Bosoi et al., 2011; De Marco et al., 2012; Frojmark et al.,
2011; Kibar et al., 2009; Kibar, Capra, & Gros, 2007; Kibar et al., 2011;
Kibar, Torban, et al., 2007; Lei et al., 2010; Robinson et al., 2012; Tao
et al., 2011
). In spite of much progress made in different organisms, the
question why hundreds of cells can adopt the uniform planar polarity still
remains to be answered. Although a long-range global cue that initiates
and establishes PCP was predicted, its nature and regulatory mechanism is
not yet clear. Therefore, the molecular nature and functional mechanisms
of the global cue are still one of the most important issues in the PCP field.
2.1. The PCP pathway
The framework of PCP was largely built from studies in
Drosophila
, in which
distally oriented bristles in the wing or ommatidia organized in a crystalline-
like array in the compound eye are most frequently studied as models of pla-
nar polarity. Polarity in other places, such as bristles on the fly abdomen and
thorax, has been also explored (
Lawrence, Casal, & Struhl, 2002, 2004;
