Biomedical Engineering Reference
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coupled with local alignment of polarity between neighboring cells
( Amonlirdviman et al., 2005 ). The model predicts the observed
interdependence of the asymmetric localization of each core PCP proteins
( Bastock, Strutt, & Strutt, 2003; Tree, Shulman, et al., 2002 ), although
depending on specific molecular mechanisms involved allows for different
degrees of residual function and polarization in the individual mutants
( Axelrod, 2009 ). The majority of this review focuses on this core signal
amplification module.
As originally proposed, a global module acts at the top of the hierarchy to
provide directional information to orient polarization with respect to the
tissue axes. In many vertebrate systems, PCP signaling relies on secreted
Wnts, leading to the proposal that a global Wnt concentration gradient
might directly provide such a directional cue ( Goodrich & Strutt, 2011;
Vladar et al., 2009; Wansleeben & Meijlink, 2011 ). The strength of the
data for these assertions varies but in at least some cases makes a
reasonably strong argument. In contrast, in Drosophila , strong evidence
argues against a direct contribution of Wnts to planar polarity ( Casal,
Struhl, & Lawrence, 2002; Chen et al., 2008; Lawrence, Casal, & Struhl,
2002 ). Instead, global directional cues are provided by a system involving
oppositely oriented gradients of differential gene expression across the
tissue axes. This module comprises the proteins Fat and Dachsous (Ft and
Ds; both atypical cadherins) and Four-jointed (Fj; a golgi ectokinase)
( Strutt, 2009 ). Ft and Ds form heterodimers that can orient in either
direction at a given cell-cell interface. Fj acts on both Ft and Ds, making
Ft a stronger ligand for Ds and Ds a weaker ligand for Ft ( Brittle, Repiso,
Casal, Lawrence, & Strutt, 2010; Simon, Xu, Ishikawa, & Irvine, 2010 ).
Ds and Fj are expressed in opposing gradients in each of the well-studied
polarizing tissues in Drosophila ( Casal et al., 2002; Ma, Yang, McNeill,
Simon, & Axelrod, 2003; Yang, Axelrod, & Simon, 2002 ) and are
proposed to result in a biased orientation of Ft-Ds heterodimers at
intercellular boundaries reflecting the direction of the Fj and Ds
expression gradients ( Simon, 2004; Strutt, 2009 ). This mechanism
produces a subtle gradient of Ft activity within each cell, and epistasis
studies in the eye suggest that Ft provides the critical output signal from
this module ( Yang et al., 2002 ). In other words, the mechanism converts
tissue-wide expression gradients into subcellular gradients of Ft activity.
A distinguishing characteristic of phenotypes displayed by global module
mutants is the presence of significant defects in planar polarity at the level of
orientation, but with essentially all cells achieving full molecular and
morphological asymmetry, thus distinguishing these mutants from mutants
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