Biomedical Engineering Reference
In-Depth Information
Are the known PCP determinants involved in recovery from kidney
injury?
Li, Kale, et al. (2009)
found that subcellular localization and levels
of expression of Fz3, a Fz shown to mediate Wnt/PCP signaling, are altered
in tubules with misoriented cell division following urinary tract obstruction,
supporting an involvement of this pathway in epithelial repair. However,
conclusive evidence of the role of PCP in repair will require assaying injured
kidneys that have had PCP determinants mutated after development is
complete.
6. CONCLUSION
PCP is currently a hot topic in the field of kidney research. However,
as frequently happens in hot fields, some of the less exciting, descriptive
work is forsaken in the attempt to be the first to publish. There are still nu-
merous, basic questions about PCP in the kidney that have not been (but in
our opinion should be) answered. Although there is increasing evidence that
PCP plays an essential role in kidney development and disease, we still do
not know what cellular processes it is controlling. Is it controlling cell elon-
gation, orientation, movement, division, or all of the above? Are different
PCP pathways affecting distinct cellular processes? Where does the signal
that establishes the direction of PCP come from? When is it established?
Does it depend on A/P patterning of the tubules? Given the expression
of numerous PCP determinants in the interstitial fibroblasts, what is the role
of this cell type in PCP? How do all the factors that affect PCP (especially,
the cystogenic factors) relate to one another and the cellular processes reg-
ulated during PCP? Polarized, subcellular localization of many PCP deter-
minants appears to be essential for their function and for PCP in flies and
other vertebrate organ systems, but such a localization pattern has so far
not been observed for any PCP proteins examined in renal tubules
(
Luyten et al., 2010
; T. J. Carroll & J. Yu, unpublished observations). Is this
aspect of PCP conserved, and if not, how is PCP established in the kidney?
We speak of CE or directed cell movements regulating diameter, but there is
actually no evidence that these movements occur and, if they do, what they
look like. Although the process of directed intercalation/CE is perfectly
plausible for a flat tissue, it does not work in a tubule as intercalation of cells
toward the top of a tubule would lead to convergence and extension on
the top side but divergence and retraction on the bottom. Clearly, a more
complicated process must be involved.
