Lack of cadherins Celsr2 and Celsr3 impairs ependymal ciliogenesis, leading to fatal hydrocephalus.
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.
Tissir
Fadel
F
Université catholique de Louvain, Institute of Neuroscience, Developmental Neurobiology, Brussels, Belgium.
Qu
Yibo
Y
Montcouquiol
Mireille
M
Zhou
Libing
L
Komatsu
Kouji
K
Shi
Dongbo
D
Fujimori
Toshihiko
T
Labeau
Jason
J
Tyteca
Donatienne
D
Courtoy
Pierre
P
Poumay
Yves
Y
Uemura
Tadashi
T
Goffinet
Andre M
AM
D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016764:Cell Polarity / Q000502:physiology; D002831:Choroid Plexus / Q000254:growth & development / Q000502:physiology; D002923:Cilia / Q000502:physiology* / Q000648:ultrastructure; D004805:Ependyma / Q000254:growth & development / Q000502:physiology* / Q000648:ultrastructure; D006849:Hydrocephalus / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D020547:Lateral Ventricles / Q000254:growth & development / Q000502:physiology / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009038:Motion; D009154:Mutation; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014741:Video Recording
D015820:Cadherins; C498478:Celsr2 protein, mouse; C444454:Celsr3 protein, mouse; D011956:Receptors, Cell Surface
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