Loss of oriented cell division does not initiate cyst formation

Saori Nishio, Xin Tian, Anna Rachel Gallagher, Zhiheng Yu, Vishal Patel, Peter Igarashi, Stefan Somlo

Research output: Contribution to journalArticle

86 Scopus citations

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, Pkhd1del4/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 Pkhd1del4/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.

Original languageEnglish (US)
Pages (from-to)295-302
Number of pages8
JournalJournal of the American Society of Nephrology
Volume21
Issue number2
DOIs
StatePublished - Feb 1 2010

ASJC Scopus subject areas

  • Nephrology

Fingerprint Dive into the research topics of 'Loss of oriented cell division does not initiate cyst formation'. Together they form a unique fingerprint.

  • Cite this