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Daple Coordinates Planar Polarized Microtubule Dynamics in Ependymal Cells and Contributes to Hydrocephalus.

Cell Rep. 2017 Jul 25;20(4):960-972
Maki Takagishi 1 , Masato Sawada 2 , Shinya Ohata 3 , Naoya Asai 4 , Atsushi Enomoto 5 , Kunihiko Takahashi 6 , Liang Weng 5 , Kaori Ushida 5 , Hosne Ara 5 , Shigeyuki Matsui 6 , Kozo Kaibuchi 7 , Kazunobu Sawamoto 8 , Masahide Takahashi 9
Maki Takagishi 1 , Masato Sawada 2 , Shinya Ohata 3 , Naoya Asai 4 , Atsushi Enomoto 5 , Kunihiko Takahashi 6 , Liang Weng 5 , Kaori Ushida 5 , Hosne Ara 5 , Shigeyuki Matsui 6 , Kozo Kaibuchi 7 , Kazunobu Sawamoto 8 , Masahide Takahashi 9
+ et al

[No authors listed]

Author information
  • 1 Department of Pathology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi 466-8550, Japan. Electronic address: m-stone@med.nagoya-u.ac.jp.
  • 2 Department of Developmental and Regenerative Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Aichi 467-8601, Japan.
  • 3 Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan; Faculty of Pharmacy, Musashino University, Shinmachi, Nishi-Tokyo, Tokyo 202-8585, Japan.
  • 4 Department of Pathology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi 466-8550, Japan; Division of Molecular Pathology, Center for Neurological Disease and Cancer, Graduate School of Medicine, Nagoya University, Nagoya, Aichi 466-8550, Japan.
  • 5 Department of Pathology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi 466-8550, Japan.
  • 6 Department of Biostatistics, Graduate School of Medicine, Nagoya University, Nagoya, Aichi 466-8550, Japan.
  • 7 Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi 466-8550, Japan.
  • 8 Department of Developmental and Regenerative Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Aichi 467-8601, Japan; Division of Neural Development and Regeneration, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan.
  • 9 Department of Pathology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi 466-8550, Japan; Division of Molecular Pathology, Center for Neurological Disease and Cancer, Graduate School of Medicine, Nagoya University, Nagoya, Aichi 466-8550, Japan. Electronic address: mtakaha@med.nagoya-u.ac.jp.

摘要


Motile cilia in ependymal cells, which line the cerebral ventricles, exhibit a coordinated beating motion that drives directional cerebrospinal fluid (CSF) flow and guides neuroblast migration. At the apical cortex of these multi-ciliated cells, asymmetric localization of planar cell polarity (PCP) proteins is required for the planar polarization of microtubule dynamics, which coordinates cilia orientation. Daple is a disheveled-associating protein that controls the non-canonical Wnt signaling pathway and cell motility. Here, we show that Daple-deficient mice present hydrocephalus and their ependymal cilia lack coordinated orientation. Daple regulates microtubule dynamics at the anterior side of ependymal cells, which in turn orients the cilial basal bodies required for the directional cerebrospinal fluid flow. These results demonstrate an important role for Daple in planar polarity in motile cilia and provide a framework for understanding the mechanisms and functions of planar polarization in the ependymal cells.

KEYWORDS: Daple, cilia, ependymal cell, hydrocephalus, planar cell polarity