The Expression and Roles of Nde1 and Ndel1 in the Adult Mammalian Central Nervous System

Z. Pei, B. Lang, Y. D. Fragoso, K. D. Shearer, L. Zhao, P. J. A. McCaffery, S. Shen, Y. Q. Ding, C. D. McCaig, J. M. Collinson

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Abstract

Mental and neurological illnesses affect one in four people. While genetic linkage analyses have shown an association of nuclear distribution factor E (NDE1, or NudE) and its ohnolog NDE-like 1 (NDEL1, or Nudel) with mental disorders, the cellular mechanisms remain unclear. In the present study, we have demonstrated that Nde1 and Ndel1 are differentially localised in the subventricular zone (SVZ) of the forebrain and the subgranular zone (SGZ) of the hippocampus, two regions where neurogenesis actively occurs in the adult brain. Nde1, but not Ndel1, is localized to putative SVZ stem cells, and to actively dividing progenitors of the SGZ. The influence of these proteins on neural stem cell differentiation was investigated by overexpression in a hippocampal neural stem cell line, HCN-A94. Increasing Nde1 expression in this neural stem cell line led to increased neuronal differentiation while decreasing levels of astroglial differentiation. In primary cultured neurons and astrocytes, Nde1 and Ndel1 were found to have different but comparable subcellular localizations. In addition, we have shown for the first time that Nde1 is heterogeneously distributed in cortical astrocytes of human brains. Our data indicate that Nde1 and Ndel1 have distinct but overlapping distribution patterns in mouse brain and cultured nerve cells. They may function differently and therefore their dosage changes may contribute to some aspects of mental disorders.
Original languageEnglish
Pages (from-to)119-136
Number of pages18
JournalNeuroscience
Volume271
Early online date29 Apr 2014
DOIs
Publication statusPublished - 20 Jun 2014

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Neural Stem Cells
Central Nervous System
Lateral Ventricles
Mental Disorders
Astrocytes
Brain
Neurons
Cell Line
Genetic Linkage
Neurogenesis
Prosencephalon
Cell Differentiation
Cultured Cells
Hippocampus
Stem Cells
Proteins

Keywords

  • expression
  • Nde1
  • Ndel1
  • adult neurogenesis
  • HCNA94
  • differentiation

Cite this

The Expression and Roles of Nde1 and Ndel1 in the Adult Mammalian Central Nervous System. / Pei, Z.; Lang, B.; Fragoso, Y. D.; Shearer, K. D.; Zhao, L.; McCaffery, P. J. A.; Shen, S.; Ding, Y. Q. ; McCaig, C. D.; Collinson, J. M.

In: Neuroscience, Vol. 271, 20.06.2014, p. 119-136.

Research output: Contribution to journalArticle

Pei, Z. ; Lang, B. ; Fragoso, Y. D. ; Shearer, K. D. ; Zhao, L. ; McCaffery, P. J. A. ; Shen, S. ; Ding, Y. Q. ; McCaig, C. D. ; Collinson, J. M. / The Expression and Roles of Nde1 and Ndel1 in the Adult Mammalian Central Nervous System. In: Neuroscience. 2014 ; Vol. 271. pp. 119-136.
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N1 - Open Access funded by Wellcome Trust Under a Creative Commons license Acknowledgments We thank Prof Angelo Sementilli, Department of Pathology, Universidade Metropolitana de Santos, SP, Brazil, for the human sample collection. This study is funded by Scottish Universities Life Sciences Alliance (HR07019 to S. Shen and C.D. McCaig), Medical Research Scotland (384 FRG to B. Lang, United Kingdom), Tenovus Scotland (G12/25 to B. Lang), Sino-UK Higher Education Research Partnership for PhD Studies (C.D. McCaig and Y.Q. Ding) and Wellcome Trust (WT081633MA-NCE to P.J.A. McCaffery, United Kingdom).

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