Biomedical Engineering Reference
In-Depth Information
part of receptor complex for the pioneer axons, while it regulates adhesion to
preexisting axons in the follower axons.
It was reported that
vang-1
/Van Gogh and
prkl-1
/Prickle as well as
dsh-1
/Dishevelled inhibit aberrant neurite formation in some motor neurons
(VC4 and VC5) (
Sanchez-Alvarez et al., 2011
). These neurons normally have
two neurites extending left-right orientation (it is not known which of them
are axons or dendrites) (
Fig. 3.7
C). In these mutants, the neurons often have
an extra neurite extending anterior-posterior orientation. These genes appear
to act in a single pathway, as double mutants among the three genes show
similar phenotype. The phenotype in
vang-1
or
prkl-1
mutants can be
suppressed by an
fmi-1
mutation, although
fmi-1
by itself does not show a phe-
notype in these neurons. Therefore,
fmi-1
appears to have an activity to pro-
mote neurite formation that is repressed by
vang-1
and
prkl-1
. Interestingly,
while
prkl-1
function is cell autonomously required in these neurons,
vang-1
and
dsh-1
can function in surrounding epithelial cells as well as in these
neurons. As PRKL-1 overexpression in the neurons can rescue
vang-1
and
dsh-1
defects, PRKL-1 is primarily responsible to inhibit neurite formation,
while
vang-1
and
dsh-1
regulate the
prkl-1
activity.
11. SUMMARY AND PERSPECTIVE
In terms of the molecular components, regulation of neurite forma-
tion by
prkl-1
,
vang-1
,
dsh-1
, and
fmi-1
most resembles to the PCP pathway
so far in
C. elegans
. However, how this regulation is related to cell polarity is
not clear yet. In contrast, global regulation of spindle orientation and polarity
of asymmetrically dividing cells by the Wnt/
b
-catenin asymmetry pathway
are conceptually quite similar to the PCP regulation, even though the
involvements of core PCP components appear to be minor and their asym-
metric localizations have not been reported. At least, Frizzled and Dishev-
elled are asymmetrically localized as in the PCP regulation in other
organisms. In
Drosophila
wing, the PCP regulation involves asymmetric cor-
tical localizations of Van Gogh and Prickle on the opposite side to those of
Frizzled and Dishevelled (
Fig. 3.1
A). Although asymmetric localizations of
their homologues have not been reported, other components of
Wnt/
b
-catenin asymmetry pathway such as WRM-1/
b
-catenin and
APR-1/APC localize to the opposite side of the Frizzled and Dishevelled
localizations (
Fig. 3.1
B). Therefore, one attractive possibility may be that
the Wnt/
b
-catenin asymmetry pathway is the origin of the PCP regulation.
During evolution, functions of WRM-1 and APR-1 might be taken over by
