Lack of cadherins Celsr2 and Celsr3 impairs ependymal ciliogenesis, leading to fatal hydrocephalus

Fadel Tissir (1) , Yibo Qu (1) , Mireille Montcouquiol (1) , Zhou Libing (1) , Kouji Komatsu (1) , Dongbo Shi (1) , Toshihiko Fujimori (1) , Jason Labeau (1) , Donatienne Tyteca (1) , Pierre Courtoy (1) , Yves Poumay (1) , Tadashi Uemura (1) , Andre M Goffinet (1)

1 Developmental Neurobiology

Ependymal cells form the epithelial lining of cerebral ventricles. Their apical surface is covered by cilia that beat coordinately to facilitate circulation of the cerebrospinal fluid. The genetic factors that govern the development and function of ependymal cilia remain poorly understood. Here we show that planar cell polarity cadherins Celsr2 and Celsr3 control these processes. In Celsr2-deficient mice, the development and planar organization of ependymal cilia are compromised, leading to defective cerebrospinal fluid dynamics and hydrocephalus. In double Celsr2+3 mutant ependyma, ciliogenesis is dramatically impaired, resulting in lethal hydrocephalus. The membrane distribution of Vangl2 and Fzd3, two key planar cell polarity proteins, is disturbed in Celsr2, and even more so in Celsr2+3 mutants. Our findings emphasize the role of planar cell polarity signaling in ependymal cilia development and function and in the pathophysiology of hydrocephalus, with possible implications in other ciliopathies.

Mots clés: Development; Differentiation; Hydrocephalus; Cell polarity

Fadel Tissir, Yibo Qu, Mireille Montcouquiol, Zhou Libing, Kouji Komatsu, et al.. Lack of cadherins Celsr2 and Celsr3 impairs ependymal ciliogenesis, leading to fatal hydrocephalus. Nature Neuroscience, 2010, ⟨10.1038/nn.2555⟩. ⟨hal-00536331⟩