Mechanosensory genes Pkd1 and Pkd2 contribute to the planar polarization of brain ventricular epithelium

Directional beating of ependymal (E) cells’ cilia in the walls of the ventricles in the brain is essential for properCSFflow.Ecells display two forms of planar cell polarity (PCP): rotational polarity of individual cilium and translational polarity(asymmetricpositioning of cilia in the apicalarea). Theorientation of individualEcells variesaccordingto their location in the ventricular wall (location-specificPCP).Ithasbeenhypothesizedthat hydrodynamic forcesonthe apical surface of radial glia cells (RGCs), theembryonic precursors of Ecells, could guide location-specificPCPin the ventricular epithelium. However, the detection mechanisms for these hydrodynamic forces have not been identified. Here, we show that the mechanosensory proteins polycystic kidney disease 1 (Pkd1) and Pkd2 are present in primary cilia of RGCs. Ablation of Pkd1 or Pkd2 in Nestin-Cre;Pkd1^flox/flox or Nestin-Cre;Pkd2^flox/flox mice, affected PCP development in RGCs and E cells. Early shear forces on the ventricular epitheliummayactivatePkd1andPkd2in primary cilia ofRGCsto properly polarizeRGCsandEcells. Consistently, Pkd1, Pkd2, or primary cilia on RGCs were required for the proper asymmetric localization of the PCP protein Vangl2 in E cells’ apical area. Analyses of single- and doubleheterozygous mutants for Pkd1 and/or Vangl2 suggest that these genes function in the same pathway to establish E cells’ PCP.Weconclude that Pkd1 and Pkd2 mechanosensory proteins contribute to the development of brain PCP and prevention of hydrocephalus.