Biomedical Engineering Reference
In-Depth Information
epithelium. It remains to be determined which Wnt pathway
Wnt11
acti-
vates in the UB cells.
Wnt11
mutants have mild branching defects similar to what is observed
in
Fat4
,
Dachs1
, and
Vangl2
mutants. Thus, it is tempting to speculate that
Wnt11
works in the same pathway as one or more of these factors to regulate
PCP. However, it is not clear how similar the defects viewed in these mu-
tants are. Further, it is not clear how noncanonical Wnt signaling relates to
the Fat/Ds or core pathways. In fact, the three pathways may function in
parallel. However, Gao et al. recently showed that
Wnt5a
, signaling through
the noncanonical receptor
Ror2
, mediated the phosphorylation and activa-
tion of Vangl2, thus demonstrating a direct connection between non-
canonical Wnt and “core” PCP signaling (
Gao et al., 2011
). The authors
suggested that the Vangl2 activity gradient was the result of aWnt5a gradient
and this process contributed to PCP.
Ror2
is expressed at high levels in the
developing kidney although kidney defects have not been described in
Ror2
mutants (
Al-Shawi, Ashton, Underwood, & Simons, 2001; Matsuda et al.,
2001
). It would be interesting to determine if a Wnt/Ror2/Vangl2 pathway
is active in the kidney.
4.4. The primary cilium
Polycystic kidney disease (PKD) is a common genetic disorder characterized
by cyst formation and overgrowth of the kidneys. Mutations in numerous
genes can cause PKD. One commonality that connects several of the gene
products is that they appear to be necessary for the formation and/or func-
tion of the primary cilia. This has led to PKD frequently being referred to as a
ciliopathy (
Hildebrandt et al., 2009; Patel et al., 2009; Sattar & Gleeson,
2011; Sharma et al., 2008; Waters & Beales, 2011
).
Over the past several years, several reports have indicated that defects in
PCP may contribute to PKD. Specifically, randomized orientation of cell
division was observed prior to overt tubular dilation in ciliary mutants
(
Fischer et al., 2006
). These data strongly suggest that the orientation in
which a cell divides contributes to the formation of a cyst. However, mis-
oriented cell division alone cannot be causal as most of the cell division that
occurs in the embryo is randomly oriented and genetic lesions have been
identified that lead to randomized cell division in tubules without cyst for-
mation (
Karner et al., 2009; Nishio et al., 2010
). Indeed, if mechanisms for
regulated cell movement and oriented cell division are both present in a
growing tubule, it would seem that defects in both processes would have
to occur to increase diameter.
