Biomedical Engineering Reference
In-Depth Information
4.2.2.2 Fz3
Fz3
has been implicated in PCP in other mouse organ systems.
Fz3
expression
levels were increased in cysts fromhumanADPKDkidneys as well as
Pkd1
mu-
tant kidneys, suggesting it may be involved in cyst progression (
Luyten et al.,
2010
). However, no single or compound mutation of Frizzleds has been
reported to result in cyst formation. Further, Fz3 levels were unchanged in
precystic
Pkd1
mutant tubules (
Luyten et al., 2010
), suggesting that, though
it may be linked to cyst expansion, it is unlikely to cause the disease.
4.2.3 Glomerulogenesis
4.2.3.1 Vangl2
Planar polarity phenomenon has not been defined in renal corpuscles, but it
is reported that its development was disrupted in
Lp
homozygotes by the
criteria of the number of capillary lumens per glomerular tuft and glomerular
tuft diameter at E18.5 (
Yates et al., 2010
). Only half of the
Lp
homozygous
mutant renal corpuscles contain two capillary lumens, and a small fraction of
glomeruli contain distorted capillary tufts, which are never observed in wild-
type kidneys. The crenellated pattern of actin filaments in podocytes is less
prominent in Lp mutants (
Yates et al., 2010
). Knockdown of
Vangl2
in
podocyte cells also leads to decreased number of cell projections, stress fibers
and cell motility (
Babayeva et al., 2011
). This suggests that tissue polarity
may be at play in some aspects of renal corpuscle maturation.
4.3. The Wnt pathway
4.3.1 Wnt7b
Wnt7b
is expressed in the nonbranching/stalk region of the collecting ducts
during the embryonic period (
Yu et al., 2009
). Ablation of
Wnt7b
results in a
failure to form a renal medulla (
Yu et al., 2009
). Prospective medullary col-
lecting ducts fail to elongate and instead become dilated. Orientation of cell
division in this segment of a wild-type ureteric epithelium is biased toward
longitudinal axis of the ducts, though the trend is not as tight as in postnatal
collecting ducts. In mutants, the orientation of cell division tends to be per-
pendicular to the longitudinal axis of the duct (
Fig. 8.3
). This suggests that
Wnt7b
regulates oriented cell division and that this process is involved in
medullary collecting duct elongation and renal medulla formation.
As mentioned, oriented cell division depends on PCP.
Wnt7b
has been
shown to be capable of activating both canonical and noncanonical signaling
in different cellular contexts (
Tu et al., 2007
). During kidney development,
Wnt7b
activates a
b
-catenin-dependent transcriptional program within the
medullary interstitium. Interestingly, Wnt7b/
b
-catenin targets
include
