The frizzled/stan Pathway and Planar Cell Polarity in the Drosophila Wing - Current Topics in Developmental Biology - page 16

being effective (as is presumably the case for fj ). Other genes would likely be
missed due to the knockdowns resulting in lethality or a loss of bristles due
to effects on the determinative cell divisions. This seems likely to be the case
for genes involved in essential basic cellular functions, and indeed genes that
are important for bristle morphogenesis such as Rab11 and exocyst
components were missed in the genome-wide screen for this reason
( Nagaraj & Adler, 2012 ). This screen has already served as a valuable source
of candidate PCP genes. For example, VhaM8.9 ( Buechling et al., 2010 )
and jitterbug (Olguin et al., 2011) were both identified in this screen and
subsequently shown in other studies to produce PCP phenotypes. It is
interesting to consider that many of the genes that produced the strongest
phenotypes in the screen have not yet been the focus of PCP papers.
A knockdown of the organic anion transporting polypeptide 30B produced the
strongest PCP phenotype (along with fz ). In the wing, a knockdown of this
gene can reverse hair polarity much as the overexpression of the spiny leg
isoform of the pk gene can. It will be interesting to see if these two proteins
function in an antagonistic way. Among the other genes where knockdowns
produced very strong phenotypes were d-Cup (a Ca þþ -binding protein),
CG17290 (which contains a gyrase motif), protein tyrosine phosphatase
69D, CG15649 (a novel protein), and CG18005 (which contains RED
domains suggesting a role in RNA splicing). The roles that these genes and
their encoded proteins play in PCP can currently only be guessed at. It is
notable that even this small set of candidate genes and proteins suggests a
wide range of biochemical functions. It seems likely that much remains to
be learned about PCP.
4. WHAT IS THE BASIS FOR THE ASYMMETRIC
LOCALIZATION OF fz/stan PATHWAY PROTEINS?
All of the fz/stan pathway proteins accumulate asymmetrically in wing
cells, with all except Stan accumulating on either the proximal or the distal cell
membrane (Stan is found on both) ( 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 )
( Fig. 1.2A ). The accumulation is uneven across these membranes. That is,
some locations along these membranes show a higher level of protein than
others and all of the fz/stan pathway proteins appear to be enriched at the
same foci on the membrane ( Fig. 1.2B ). This suggests that the proteins