Biomedical Engineering Reference
In-Depth Information
cytoskeleton was activated in the vicinity of the distal most vertex to promote
hair outgrowth and this resulted in a hair that grewdistally. Further, mutations
in all of the
fz
pathway genes resulted in hairs forming at an alternative
subcellular location. An important insight from the analysis of the pupal
phenotype was that the
fz/stan
pathway regulated hair initiation.
The observation that
fz
pathway proteins accumulated asymmetrically in
wing cells was first observed by Uemura and colleagues studying the
stan/
flamingo
gene (
Usui et al., 1999
) and this breakthrough opened up a new stage
in PCP research (
Fig. 1.2A and B
). Over the next few years, similar results
were obtained for all of the
fz/stan
pathway proteins (
Adler et al., 2004;
Axelrod, 2001; Bastock et al., 2003; Feiguin et al., 2001; Shimada et al.,
2001; Strutt, 2001; Strutt & Warrington, 2008; Tree et al., 2002; Usui
et al., 1999; Yan et al., 2008
). Further biochemical experiments
established that several pairs of these proteins could interact directly with
one another (
Bastock et al., 2003; Das et al., 2004; Jenny et al., 2003,
2005; Lu et al., 2010; Wong et al., 2003
). A more detailed discussion of
the function of these genes and how the asymmetric accumulation of the
proteins is achieved is presented later.
The
fz/stan
pathway functions to limit the region of the cell where the
cytoskeleton is activated to form a hair. Neither are all wing cells of the same
size, nor are all epithelial cells in other body regions of the same size or shape
as wing cells. Further, nutrition and the temperature during development
can alter cell size without altering planar polarity. Hence, the pathway
has the ability to scale and function in a variety of cell geometries. It is clear,
however, that this ability is not infinite. Cells that are much larger than nor-
mal can arise from the cells being polyploidy or stretched due to wound
healing. Both of these conditions result in the cells often forming multiple
hairs that can be of abnormal polarity (
Adler, Liu, & Charlton, 2000
). The
fz/stan
pathway is still functioning in these large cells, but it is unable to reg-
ulate the cytoskeleton well enough so that a single distally pointing hair is
produced.
3.2. ds/ft pathway
Mutations in several other groups of genes also give rise to PCP phenotypes.
The atypical cadherins
dachsous
and
fat
and the Golgi kinase
four jointed
were
first discovered to result in PCP phenotypes due to their leg joint pheno-
types (
Held et al., 1986
). Later, it was established that they were also required
for wing and eye PCP (
Adler et al., 1998; Matakatsu & Blair, 2004; Simon,
2004; Zeidler et al., 1999
). A variety of evidence indicates that Ft and Ds act
