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Loss of oriented cell division does not initiate cyst formation. | LitMetric

Loss of oriented cell division does not initiate cyst formation.

J Am Soc Nephrol

Section of Nephrology, Yale University School of Medicine, P.O. Box 208029, 333 Cedar Street, New Haven, CT 06520-8029, USA.

Published: February 2010

AI Article Synopsis

Article Abstract

Polycystic kidney disease (PKD) can arise from either developmental or postdevelopmental processes. Recessive PKD, caused by mutations in PKHD1, is a developmental defect, whereas dominant PKD, caused by mutations in PKD1 or PKD2, occurs by a cellular recessive mechanism in mature kidneys. Oriented cell division is a feature of planar cell polarity that describes the orientation of the mitotic axes of dividing cells during development with respect to the luminal vector of the elongating nephron. In polycystic mutant mice, the loss of oriented cell division may also contribute to the pathogenesis of PKD. Here, we examined the role of oriented cell division in mouse models based on mutations in Pkd1, Pkd2, and Pkhd1. Precystic tubules after kidney-selective inactivation of either Pkd1 or Pkd2 did not lose oriented division before cystic dilation but lost oriented division after tubular dilation began. In contrast, Pkhd1(del4/del4) mice lost oriented cell division but did not develop kidney cysts. Increased intercalation of cells into the plane of the tubular epithelium maintained the normal tubular morphology in Pkhd1(del4/del4) mice, which had more cells present in transverse tubular profiles. In conclusion, loss of oriented cell division is a feature of Pkhd1 mutation and cyst formation, but it is neither sufficient to produce kidney cysts nor required to initiate cyst formation after mutation in Pkd1 or Pkd2.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834544PMC
http://dx.doi.org/10.1681/ASN.2009060603DOI Listing

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