Biomedical Engineering Reference
In-Depth Information
Potential mechanisms by which the global module, as well as additional
unidentified global cues, might transmit directional information to the core
module remain poorly understood. One plausible postulate derives from the
observation of a polarized apical microtubule network that is seen to have a
slight excess of plus-ends on one side of the cell (
Eaton, Wepf, & Simons,
1996; Shimada, Yonemura, Ohkura, Strutt, & Uemura, 2006
). Vesicles
containing Fz have been observed to traverse the cell in a microtubule-
dependent fashion, moving in a plus-end-biased direction (
Shimada et al.,
2006
). Preliminary evidence suggests that the subcellular Ft gradient
produced by the action of graded Ds and Fj expression (and recently
visualized where the gradients are steep;
Brittle et al., 2012
) may produce
the bias of this microtubule network. Perturbation of Ds, both by
mutation and overexpression, produces alteration of microtubule
orientation, providing at least some evidence that the global module
orients the core module by organizing microtubules (
Harumoto et al.,
2010
). Although appealing, this potential mechanism requires substantial
additional validation. Whether additional unidentified global cues might
work through regulating apical microtubules remains purely speculative.
At the bottom of the hierarchy reside the tissue-specific effectors.
Distinct sets of components are responsible for translating the molecular asym-
metry of the core PCP proteins to the specific polarized outputs required in
each tissue. These range from asymmetric cytoskeletal organization to asym-
metric cell fate determination. Mutating these components therefore causes
planar-polarization defects of certain structures. Because these effectors are
at the bottom of the hierarchy, their malfunction, in general, affects the
polarized readouts without compromising the protein asymmetry, and thus
the function, of the core PCP genes (
Adler, Zhu, & Stone, 2004
). Recently,
some core PCP proteins have been suggested to be directly involved in
polarizing cellular structures. For example, in vertebrate multiciliated cells,
Dvl2 (a Dsh homologue) is associated with basal bodies of apical motile cilia,
though direct evidence that it contributes to polarization of those cilia is thus
far lacking (
Park, Mitchell, Abitua, Kintner, & Wallingford, 2008
).
2.2. Reasons to reconsider?
A three-tiered hierarchy was initially proposed based on a variety of obser-
vations. The core module was proposed to regulate the tissue-specific com-
ponents in part based on their tissue specificity (
Adler, Taylor, & Charlton,
2000; Lee & Adler, 2002; Strutt, Johnson, Cooper, & Bray, 2002
) and on
