Interaction between FEZ1 and DISC1 in regulation of neuronal development and risk for schizophrenia

Eunchai Kang, Katherine E Burdick, Ju Young Kim, Xin Duan, Junjie U Guo, Kurt A Sailor, Dhong-Eun Jung, Sundar Ganesan, Sungkyung Choi, Dennis Pradhan, Bai Lu, Dimitrios Avramopoulos, Kimberly Christian, Anil K Malhotra, Hongjun Song, Guo-li Ming

Research output: Contribution to journalArticlepeer-review

76 Citations (Scopus)


Disrupted-in Schizophrenia 1 (DISC1), a susceptibility gene for major mental disorders, encodes a scaffold protein that has a multifaceted impact on neuronal development. How DISC1 regulates different aspects of neuronal development is not well understood. Here, we show that Fasciculation and Elongation Protein Zeta-1 (FEZ1) interacts with DISC1 to synergistically regulate dendritic growth of newborn neurons in the adult mouse hippocampus, and that this pathway complements a parallel DISC1-NDEL1 interaction that regulates cell positioning and morphogenesis of newborn neurons. Furthermore, genetic association analysis of two independent cohorts of schizophrenia patients and healthy controls reveals an epistatic interaction between FEZ1 and DISC1, but not between FEZ1 and NDEL1, for risk of schizophrenia. Our findings support a model in which DISC1 regulates distinct aspects of neuronal development through its interaction with different intracellular partners and such epistasis may contribute to increased risk for schizophrenia.

Original languageEnglish
Pages (from-to)559-71
Number of pages13
Issue number4
Early online date16 Nov 2011
Publication statusPublished - 16 Nov 2011
Externally publishedYes

Bibliographical note

Copyright © 2011 Elsevier Inc. All rights reserved.

Acknowledgements: We thank D. Weinberg, D. Valle, and members of Ming and Song Laboratories for critical comments, L. Liu, Y. Cai, and H. Qasim for technical support, and A. Sawa and A. Kamiya for anti-NDEL1 antibodies. This work was supported by NIH (NS048271, HD069184), NARSAD, and MSCRF to G.-l.M., by NIH (NS047344, AG024984, MH084018, MH087874), IMHRO and Johns Hopkins BSI to H.S., by MH79800, MH080173 and the Donald and Barbara Zucker Foundation to A.K.M., and by MH077807 to K.E.B., J.Y.K., and K.C. were partially supported by postdoctoral fellowships from MSCRF.


  • Adaptor Proteins, Signal Transducing/deficiency
  • Adult
  • Aged
  • Animals
  • Case-Control Studies
  • Cells, Cultured
  • Female
  • Gene Knockdown Techniques
  • Genetic Association Studies
  • Hippocampus/growth & development
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Nerve Tissue Proteins/deficiency
  • Neurogenesis/genetics
  • Polymorphism, Single Nucleotide/genetics
  • Protein Binding/genetics
  • Risk Factors
  • Schizophrenia/genetics


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