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2011 ; 3
(5
): 588-605
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Modeling the control of planar cell polarity
#MMPMID21755606
Axelrod JD
; Tomlin CJ
Wiley Interdiscip Rev Syst Biol Med
2011[Sep]; 3
(5
): 588-605
PMID21755606
show ga
A growing list of medically important developmental defects and disease
mechanisms can be traced to disruption of the planar cell polarity (PCP) pathway.
The PCP system polarizes cells in epithelial sheets along an axis orthogonal to
their apical-basal axis. Studies in the fruitfly, Drosophila, have suggested that
components of the PCP signaling system function in distinct modules, and that
these modules and the effector systems with which they interact function together
to produce emergent patterns. Experimental methods allow the manipulation of
individual PCP signaling molecules in specified groups of cells; these
interventions not only perturb the polarization of the targeted cells at a
subcellular level, but also perturb patterns of polarity at the multicellular
level, often affecting nearby cells in characteristic ways. These kinds of
experiments should, in principle, allow one to infer the architecture of the PCP
signaling system, but the relationships between molecular interactions and
tissue-level pattern are sufficiently complex that they defy intuitive
understanding. Mathematical modeling has been an important tool to address these
problems. This article explores the emergence of a local signaling hypothesis,
and describes how a local intercellular signal, coupled with a directional cue,
can give rise to global pattern. We will discuss the critical role mathematical
modeling has played in guiding and interpreting experimental results, and
speculate about future roles for mathematical modeling of PCP. Mathematical
models at varying levels of inhibition have and are expected to continue
contributing in distinct ways to understanding the regulation of PCP signaling.