Biomedical Engineering Reference
In-Depth Information
Additional cell-autonomous mechanisms are likely required by each
polarizing cell to interpret and transduce directional signals from the global
module, or from other sources of directional information, to downstream
modules. Some recent results suggest that a polarized apical microtubule net-
work in fly wing cells may be oriented by signals from the global module and
in turn influence directional trafficking of vesicles containing core PCP
proteins (
Harumoto et al., 2010
). Whether and how this aspect of
cell-autonomous regulation contributes to the establishment of core PCP
protein asymmetry awaits more detailed exploration.
4.4. Building a unifying mechanism
Given the robust establishment of asymmetric core PCP protein localization
in numerous polarized cell types in the animal kingdom, we postulate that
the set of cell-autonomous and nonautonomous mechanisms described
in this review are conserved, at least in their essential mechanistic logic.
During the decade, as PCP protein localization asymmetry was initially dis-
covered, the contribution of this process to the establishment of asymmetry
has been intensively studied. Mechanistic molecular details of many of these
processes have begun to emerge. Yet, despite the considerable progress, a
relatively large amount is still to be learned about this fascinating process.
Genetic experiments, relying heavily on clonal analyses, have led to a
model of the core PCP mechanism in which asymmetric complexes assem-
bled between neighboring cells transmit polarity information between cells,
serving both to amplify asymmetry once it is initiated and to produce local
polarity alignment between neighbors. Based on this basic biological prin-
ciple, mathematical modeling, in various forms, has shown by mimicking
the characteristic patterns of PCP protein localization in wild-type as well
as mutant genetic mosaic wings that this kind of mechanism is a plausible
description of how the core PCP module functions (
Amonlirdviman
et al., 2005; Burak & Shraiman, 2009; Le Garrec, Lopez, & Kerszberg,
2006; Schamberg, Houston, Monk, & Owen, 2010; Webb & Owen,
2004; Zhu, 2009
). By continuing to combine modeling with biological
experimentation, it should be possible to derive a much deeper
understanding of the specific molecular interactions that underlie the
feedback mechanism.
The nature of the global directional cue remains controversial. While we
prefer a series model in which overall directional information comes from
the Ft/Ds/Fj module and acts to bias the directionality of the core module,
