Biomedical Engineering Reference
In-Depth Information
between core PCP proteins across cell membrane and how such cell-cell
interaction forms a positive-feedback loop to reinforce and amplify the
polarization of these core PCP proteins within individual cells (
Axelrod,
2009; Chen et al., 2008; Wu & Mlodzik, 2008
). However, prior to the
amplification of polarization, the symmetrical localization of core PCP
proteins must be altered. More importantly, PCP must be established in a
field of cells in a three-dimensional tissue or organ. A distinct character of
PCP is uniformity in a large filed of cells, which requires not only local
coordination between cells but also a global directional cue. For instance,
it was unknown why mesenchymal cells in the limb establish PCP along
P-D, not A-P axis; why skin hairs orient away from the head and why
cilia are localized posteriorly in the node. The global module introduces
mechanisms to link the global direction of PCP to the tissue axes.
Among these mechanisms, Ft (Fat)/Ds (Daschous)/Fj (Four-jointed)
system has been proposed to act upstream of PCP to provide a
directional cue and these work is mostly done in the context of the
Drosophila
wing hair polarity (
Adler, Charlton, & Liu, 1998; Casal,
Struhl, & Lawrence, 2002; Ma, Yang, McNeill, Simon, & Axelrod, 2003;
Yang, Axelrod, & Simon, 2002; Zeidler, Perrimon, & Strutt, 2000
). This
system consists of proximally expressed protocadherin Ft, protocadherin
Ds, and distally expressed Golgi-resident kinase Fj. Ft and Ds form
heterodimers across cell membrane, and Fj phosphorylates them to
modulate their binding. The graded expression of Ds and Fj results in the
biased Ft/Ds heterodimer formation along P-D axis in the fly wing,
providing an instructive cue to convey the directional information from
Ds/Fj transcriptional gradient to downstream PCP components.
However, how Ds/Fj signal is transmitted to core PCP proteins is
completely unknown and other evidence supported a model in which
Ft/Ds/Fj system and core PCP proteins function in parallel (
Casal,
Lawrence, & Struhl, 2006; Lawrence et al., 2007
). In addition, it is
unknown what sets up the graded expression of Ds/Fj. In mammals,
mutants of Ft/Ds/Fj components display either no or mild PCP
phenotypes (
Ciani, Patel, Allen, & ffrench-Constant, 2003; Mao et al.,
2011; Probst, Rock, Gessler, Vortkamp, & Puschel, 2007; Saburi et al.,
2008; Saburi, Hester, Goodrich, & McNeill, 2012
). Notably, this system
may also regulate another fundamentally important signaling pathway, the
Hippo pathway, which controls organ size through regulating cell
proliferation and apoptosis. Therefore, it becomes challenging to clearly
separate their
roles
in PCP and Hippo (
Matakatsu & Blair, 2012
).
