¹Renal Division, University Hospital Freiburg, Freiburg, Germany

Correspondence: M Simons and G Walz, Renal Division, University Hospital Freiburg, Hugstetter Strasse 55, Freiburg, 79106 Germany. E-mail: matias.simons@mssm.edu and gerd.walz@uniklinik-freiburg.de

²Current address: Mount Sinai School of Medicine, Brookdale Department of Molecular Cell and Developmental Biology, One Gustave L. Levy Place, New York City, New York 10029, USA

Received 14 December 2005; Revised 7 March 2006; Accepted 21 March 2006; Published online 28 June 2006.

Abstract

Polycystic kidneys are caused by an amazingly broad array of genetic mutations and manipulations. The ciliary hypothesis has evolved as the unifying concept of cystogenesis: cilia, bend by fluid flow, initiate a calcium influx that prevents cyst formation. The integrity of ciliary functions has been linked to the polycystic kidney disease gene products localizing to the cilium or the basal body/centrosome. Until recently, the signals and cellular programs located downstream of the ciliary-mediated calcium flux have remained elusive. Now, several reports point towards a role of the cilium or the basal body/centrosome complex in planar cell polarity, a pathway that orients cell in the plane of a tissue layer. First, Inversin, a protein mutated in nephronophthisis type II was found to act as a switch between the canonical and the noncanonical Wnt cascade, suggesting that -catenin/TCF-dependent gene transcription has to be curtailed to allow normal tubular differentiation. Second, heterozygote deletions of Bardet–Biedl syndrome proteins affect neural tube closure and disrupt the cochlear sterociliary bundles, two typical planar cell polarity defects. Third, tubular epithelial cells undergo oriented cell division during tubular elongation, along the axis of the anterior–posterior axis of the nephron. Thus, the cilium or the basal body/centrosome complex may provide the spatial cues to position the centrosome and the mitotic spindle before the next cell division. Failure to communicate this spatial information may condemn the tubular epithelial cells to proliferate and to form cysts.