Biomedical Engineering Reference
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however, the mutants of the core module selected for these experiments
might not fully abolish core module function, and therefore, the
observed results could be compatible with either a linear or nonlinear
(parallel) architecture between the modules. Given the available evidence,
we think that the linear model remains most valid as a blueprint of the
relationship between modules, but it is likely that only the emergence of
molecular-level understanding of signal transmission between modules
will solidify (or eliminate) the linear three-tiered model. A more detailed
discussion of this problem has been published elsewhere (
Axelrod, 2009
).
A summary of the revised hierarchical model as described earlier can be
found in
Fig. 2.1
.
3. ASYMMETRIC PROTEIN LOCALIZATION: A HALLMARK
OF PCP
Because regular planar-polarized arrays of asymmetrically constructed
cellular structures on the surface of epithelial cells have been appreciated for
some time, the asymmetrically localized distribution of core PCP proteins
suggested a striking feature of the PCP signaling mechanism that might
underlie the molecular polarization of these cells. Indeed, we now believe
that the segregation of these proteins to opposite sides of the cell is intimately
linked to the mechanism that amplifies an initial input bias and locally aligns
polarity between cells. Since its initial discovery in the
Drosophila
pupal wing
epithelium (
Axelrod, 2001; Strutt, 2001
), similar asymmetrically localized
distributions of core PCP proteins have been found in a substantial
number of planar-polarized epithelial
types in both invertebrates and
vertebrates.
In the developing fly eye disk, PCP proteins are found differentially
enriched at the adherens junction between the two cells that will differentiate
asymmetrically to become the R3 and R4 photoreceptor cells in each devel-
oping ommatidium (
Das, Reynolds-Kenneally, & Mlodzik, 2002; Rawls
& Wolff, 2003; Strutt et al., 2002
). The enrichment of the Fz/Dsh
complex on the prospective R3 cell side is thought to impose an initial
bias that inhibits Notch signaling in this cell, biasing the asymmetric, lateral
inhibition-mediated R3/R4 fate decision between the two equipotent
precursors (
Strutt et al., 2002
). Asymmetric PCP protein localization
was also found in the sensory organ precursor (SOP) cells on the
developing thorax (
Bellaiche, Beaudoin-Massiani, Stuttem, & Schweisguth,
2004; Bellaiche, Gho, Kaltschmidt, Brand, & Schweisguth, 2001
). Vang
