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

F Tissir, Y Qu, M Montcouquiol, L Zhou… - Nature …, 2010 - nature.com
F Tissir, Y Qu, M Montcouquiol, L Zhou, K Komatsu, D Shi, T Fujimori, J Labeau, D Tyteca
Nature neuroscience, 2010nature.com
Ependymal cells form the epithelial lining of cerebral ventricles. Their apical surface is
covered by cilia that beat in a coordinated fashion to facilitate circulation of the cerebrospinal
fluid (CSF). The genetic factors that govern the development and function of ependymal cilia
remain poorly understood. We found that the 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 CSF dynamics and …
Abstract
Ependymal cells form the epithelial lining of cerebral ventricles. Their apical surface is covered by cilia that beat in a coordinated fashion to facilitate circulation of the cerebrospinal fluid (CSF). The genetic factors that govern the development and function of ependymal cilia remain poorly understood. We found that the 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 CSF dynamics and hydrocephalus. In Celsr2 and Celsr3 double mutant ependyma, ciliogenesis is markedly impaired, resulting in lethal hydrocephalus. The membrane distribution of Vangl2 and Fzd3, two key planar cell polarity proteins, was disturbed in Celsr2 mutants, and even more so in Celsr2 and Celsr3 double mutants. Our findings suggest that planar cell polarity signaling is involved in ependymal cilia development and in the pathophysiology of hydrocephalus, with possible implications in other ciliopathies.
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