Loss of Dishevelleds disrupts planar polarity in ependymal motile cilia and results in hydrocephalus

Neuron. 2014 Aug 6;83(3):558-71. doi: 10.1016/j.neuron.2014.06.022. Epub 2014 Jul 18.


Defects in ependymal (E) cells, which line the ventricle and generate cerebrospinal fluid flow through ciliary beating, can cause hydrocephalus. Dishevelled genes (Dvls) are essential for Wnt signaling, and Dvl2 has been shown to localize to the rootlet of motile cilia. Using the hGFAP-Cre;Dvl1(-/-);2(flox/flox);3(+/-) mouse, we show that compound genetic ablation of Dvls causes hydrocephalus. In hGFAP-Cre;Dvl1(-/-);2(flox/flox);3(+/-) mutants, E cells differentiated normally, but the intracellular and intercellular rotational alignments of ependymal motile cilia were disrupted. As a consequence, the fluid flow generated by the hGFAP-Cre;Dvl1(-/-);2(flox/flox);3(+/-) E cells was significantly slower than that observed in control mice. Dvls were also required for the proper positioning of motile cilia on the apical surface. Tamoxifen-induced conditional removal of Dvls in adult mice also resulted in defects in intracellular rotational alignment and positioning of ependymal motile cilia. These results suggest that Dvls are continuously required for E cell planar polarity and may prevent hydrocephalus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Animals
  • Cell Polarity / genetics
  • Cell Polarity / physiology*
  • Cilia / genetics
  • Cilia / pathology*
  • Dishevelled Proteins
  • Ependyma / pathology*
  • Hydrocephalus / etiology*
  • Hydrocephalus / genetics
  • Hydrocephalus / pathology
  • Mice
  • Mice, Transgenic
  • Phosphoproteins / genetics*
  • Signal Transduction / genetics
  • Signal Transduction / physiology*


  • Adaptor Proteins, Signal Transducing
  • DVL1 protein, human
  • DVL2 protein, human
  • Dishevelled Proteins
  • Dvl1 protein, mouse
  • Dvl2 protein, mouse
  • Phosphoproteins