Biomedical Engineering Reference
In-Depth Information
junction. These genes appear to act after hair outgrowth, and unlike the
fz/
stan
pathway, mutations in these genes do not result in cells forming multiple
hairs. The asymmetric localization of Dsh is not altered in a Gli mutant, and
the localization of Coracle is not affected by mutations in
fz/stan
genes
(
Venema et al., 2004
#71). Further, double mutants of septate junction
and
fz/stan
genes show an additive phenotype consistent with their
functioning in parallel. How the septate junction genes function in PCP
has not been extensively studied. It is also not clear if this set of genes is
needed for PCP in other contexts in Drosophila or in other organisms.
3.4. Other genes that impact PCP
In recent years, many additional genes have been identified that are required
for PCP in the fly. The literature is somewhat inconsistent as to the prop-
erties of a gene required to consider it a PCP gene. Some authors require a
hair/bristle orientation phenotype (or ommatidia of the incorrect chiral
type), while others have simply required cells form multiple hairs (of normal
orientation) or result in misrotated ommatidia of the correct chiral type. As is
discussed in more detail below, many aspects of general cell biology are
likely involved in polarizing cells; hence, it is not surprising that genes that
encode a wide variety of protein types and functions have been found to
produce PCP phenotypes. These include some that might be thought of
as having rather general functions. Not surprisingly, these genes differ from
those of the
fz/stan
pathway components in being much less specific with
regard to their mutant phenotypes. The collection of genes includes ones
that encode proteins that function in intracellular trafficking such as
Rab23
(
Pataki et al., 2010
),
Rab5
(
Purvanov, Koval, & Katanaev, 2010
),
and the Rab5 effector
Rabenosyn-5
(
Mottola, Classen, Gonzalez-Gaitan,
Eaton, & Zerial, 2010
). Mutations in genes that encode proteins that func-
tion to promote actin filament disassembly
twinstar
(
cofilin
)(
Blair et al., 2006
)
and
flare
(
AIP1
)(
Ren, Charlton, & Adler, 2007
) have been found to result in
PCP phenotypes and disruptions in the normal asymmetric accumulation of
fz/stan
pathway proteins. Also implicated in PCP are genes that encode tran-
scription regulators such as
grainy head
(
grh
)(
Lee & Adler, 2004
) and
atrophin
(
Fanto et al., 2003
); kinases such as
misshapened
(
Paricio, Feiguin, Boutros,
Eaton, & Mlodzik, 1999
),
Rho Kinase
(
Winter et al., 2001
), the Abelson ty-
rosine kinase (
Singh, Yanfeng, Grumolato, Aaronson, & Mlodzik, 2010
),
aPKC
(
Djiane, Yogev, & Mlodzik, 2005
),
casein kinase I
(
Strutt, Price, &
Strutt, 2006
), and the
gilgamesh
kinase (
Gault, Olguin, Weber, & Mlodzik,
2012
); the
Widerborst
phosphatase (
Hannus, Feiguin, Heisenberg, & Eaton,
