SNX27 deletion causes hydrocephalus by impairing ependymal cell differentiation and ciliogenesis

Xin Wang, Ying Zhou, Jian Wang, I. Chu Tseng, Timothy Huang, Yingjun Zhao, Qiuyang Zheng, Yue Gao, Hong Luo, Xian Zhang, Guojun D Bu, Wanjin Hong, Huaxi Xu

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Hydrocephalus is a brain disorder derived from CSF accumulation due to defects in CSF clearance. Although dysfunctional apical cilia in the ependymal cell layer are causal to the onset of hydrocephalus, mechanisms underlying proper ependymal cell differentiation are largely unclear. SNX27 is a trafficking component required for normal brain function and was shown previously to suppress γ-secretase-dependent amyloid precursor protein and Notch cleavage. However, it was unclear how SNX27-dependent γ-secretase inhibition could contribute to brain development and pathophysiology. Here, we describe and characterize an Snx27- deleted mouse model for the ependymal layer defects of deciliation and hydrocephalus. SNX27 deficiency results in reductions in ependymal cells and cilia density, as well as severe postnatal hydrocephalus. Inhibition of Notch intracellular domain signaling with γ-secretase inhibitors reversed ependymal cells/cilia loss and dilation of lateral ventricles in Snx27-deficient mice, giving strong indication that Snx27 deletion triggers defects in ependymal layer formation and ciliogenesis through Notch hyperactivation. Together, these results suggest that SNX27 is essential for ependymal cell differentiation and ciliogenesis, and its deletion can promote hydrocephalus pathogenesis.

Original languageEnglish (US)
Pages (from-to)12586-12597
Number of pages12
JournalJournal of Neuroscience
Volume36
Issue number50
DOIs
StatePublished - Dec 14 2016
Externally publishedYes

Keywords

  • Cilia
  • Ependymal cell
  • Hydrocephalus
  • SNX27
  • Trafficking
  • γ-secretase

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'SNX27 deletion causes hydrocephalus by impairing ependymal cell differentiation and ciliogenesis'. Together they form a unique fingerprint.

  • Cite this

    Wang, X., Zhou, Y., Wang, J., Tseng, I. C., Huang, T., Zhao, Y., Zheng, Q., Gao, Y., Luo, H., Zhang, X., Bu, G. D., Hong, W., & Xu, H. (2016). SNX27 deletion causes hydrocephalus by impairing ependymal cell differentiation and ciliogenesis. Journal of Neuroscience, 36(50), 12586-12597. https://doi.org/10.1523/JNEUROSCI.1620-16.2016