Biomedical Engineering Reference
In-Depth Information
formation, a distinct phase of cell intercalation and cell rearrangement is ob-
served that drives the renal tubule elongation and narrows the renal tubule
diameter from 6-10 cells to 2 cells surrounding the lumen (
Jung, Denholm,
Skaer, & Affolter, 2005
and references therein). Though the molecular ma-
chinery is not well characterized, nonmuscle myosin II heavy chain, a gene
involved in multicellular rosette formation and resolution during Drosophila
germband extension, has been implicated in this process.
After birth and for the first several weeks of life,
Fischer et al. (2006)
reported that the tubules of the kidney (both the nephrons and the collecting
ducts) continue to elongate, while the number of cells in the circumference
remains fairly constant. By following the progeny of individually labeled
postnatal tubule cells over a period of 5 weeks, they noticed little divergent
cell migration or nonclonal cell intercalation. They concluded that, at least
in a normal postnatal tubule, CE/cellular intercalation is unlikely to be in-
volved in maintenance of tube diameter. However, measurement of mitotic
angles in outer medullary Aqp2
þ
(collecting ducts), uromodulin
þ
(ascend-
ing limb of loops-of-Henle), or Lotus tetragonolobus (LTL)
(proximal tu-
bules) tubules identified rigorously oriented cell division (
Fig. 8.2
) along the
proximal/distal axis of tubules such that 95% of the mitotic angles were
within 34
and the average is 11
. This finding suggests that oriented cell
division drives tubule elongation and diameter establishment during postna-
tal tubular development.
Yu et al. (2009)
found a similar process was in-
volved in the growth of the renal papilla. Thus, oriented cell divisions
appear to be essential for much of the growth that drives the ultimate shape
of the kidney.
Interestingly,
Luyten et al. (2010)
found that the average number of cells
in the circumference of the collecting duct continues to decrease postnatally,
suggesting that some intercalation continues after birth. The apparent dis-
crepancy in the involvement of cell intercalation in postnatal collecting ducts
in regard with the findings of Fischer et al. and Luyten et al. remains to be
resolved. Although the observations of Fischer et al. could be explained if
cell intercalation in collecting ducts is clonal, this explanation cannot explain
a decrease in circumference.
Pkd1
mutant cells displayed reduced rates in
scattered cell migration in the
in vitro
wound healing assay, suggesting that
defective cell intercalation may contribute to cyst formation in
Pkd1
mutants
and PC1 plays a role in regulating cell intercalation (
Luyten et al., 2010
).
Thus, it appears that the ultimate length and diameter of the kidney tubules
depend on a combination of directed cell movements and oriented cell
divisions.
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