Biomedical Engineering Reference
In-Depth Information
contains a HRM which may bind putative ligands, although none has been
identified thus far.
Celsr
genes were first identified in mice (
Hadjantonakis et al., 1997
).
They form a highly conserved family with homologs in ascidians, worms,
flies, and vertebrates. The fruit fly Celsr ortholog was cloned independently
by two groups and is known as
Flamingo
(
Fmi
)or
Starry night
(
Stan
)(
Chae
et al., 1999; Usui et al., 1999
). Genetic studies have established a critical
role for
Fmi/Stan
in planar cell polarity (PCP) events, particularly in the
stereotypic organization of wing hairs (trichomes) and sensory bristles
(
Chae et al., 1999; Usui et al., 1999
), the alignment of ommatidia in the
eye (
Mlodzik, 1999
), and the asymmetric division of sensory organ
precursors (
Bellaiche, Gho, Kaltschmidt, Brand, & Schweisguth, 2001;
Segalen & Bellaiche, 2009
). In these processes, Fmi/Stan interacts
genetically and functionally with so-called core PCP proteins. Drosophila
core PCP proteins include serpentine receptors Frizzled (fz and fz2 are
partially redundant in PCP); the tetraspannin Van Gogh (vang, also
named strabismus); and the three cytoplasmic proteins Disheveled (dsh),
Prickle (pk), and Diego (dgo) (
Adler, 2002; Feiguin, Hannus, Mlodzik, &
Eaton, 2001; Gubb et al., 1999; Strutt, Johnson, Cooper, & Bray, 2002;
Taylor, Abramova, Charlton, & Adler, 1998; Wolff & Rubin, 1998
). In
the insect wing, the distribution of core PCP proteins is tightly and
dynamically regulated. Initially distributed in all apical junctions, they
adopt a transient polarized partition along the proximal-distal axis shortly
before the growth of wing hairs, and this partition is essential to the
establishment of polarity and the proper orientation of hairs. fmi/stan,
fzd, dsh, and dgo are enriched at the distal border of wing cells, whereas
fmi/stan, vang, and pk are enriched at the proximal border (
Bastock,
Strutt, & Strutt, 2003; Jenny, Darken, Wilson, & Mlodzik, 2003; Usui
et al., 1999
). Given that fmi/stan localizes to both proximal and distal
junctions, it was considered a permissive molecule with no active effect
on polarity: fmi/stan homodimers would act as a scaffold, promoting cell
adhesion and bridging the distal (fz-expressing) side of a cell and the
proximal (vang-expressing) side of the adjacent cell. However, more
recent data provide evidence that fmi/stan plays an instructive role: its
central portion containing the HRM and TM domains interacts
physically with fz. Furthermore, fmi/stan selectively recruits fz and vang
to opposite cell boundaries, thereby initiating bidirectional polarity signals
(
Chen et al., 2008
). In line with this, genetic analyses in flies
demonstrated a mutual requirement for fmi/stan, fz, and dsh to achieve a
