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author:

Xu, D. (Xu, D..) [1] | Yao, M. (Yao, M..) [2] | Wang, Y. (Wang, Y..) [3] | Yuan, L. (Yuan, L..) [4] | Hoeck, J.D. (Hoeck, J.D..) [5] | Yu, J. (Yu, J..) [6] | Liu, L. (Liu, L..) [7] | Yeap, Y.Y.C. (Yeap, Y.Y.C..) [8] | Zhang, W. (Zhang, W..) [9] | Zhang, F. (Zhang, F..) [10] | Feng, Y. (Feng, Y..) [11] | Ma, T. (Ma, T..) [12] | Ng, D.C.H. (Ng, D.C.H..) [14] | Niu, X. (Niu, X..) [15] | Su, B. (Su, B..) [16] | Behrens, A. (Behrens, A..) [17] | Xu, Z. (Xu, Z..) [18]

Indexed by:

Scopus

Abstract:

Mutations of WD repeat domain 62 (WDR62) lead to autosomal recessive primary microcephaly (MCPH), and down-regulation of WDR62 expression causes the loss of neural progenitor cells (NPCs). However, how WDR62 is regulated and hence controls neurogenesis and brain size remains elusive. Here, we demonstrate that mitogen-activated protein kinase kinase kinase 3 (MEKK3) forms a complex with WDR62 to promote c-Jun N-terminal kinase (JNK) signaling synergistically in the control of neurogenesis. The deletion of Mekk3, Wdr62, or Jnk1 resulted in phenocopied defects, including premature NPC differentiation. We further showed that WDR62 protein is positively regulated by MEKK3 and JNK1 in the developing brain and that the defects of wdr62 deficiency can be rescued by the transgenic expression of JNK1. Meanwhile, WDR62 is also negatively regulated by T1053 phosphorylation, leading to the recruitment of F-box and WD repeat domain-containing protein 7 (FBW7) and proteasomal degradation. Our findings demonstrate that the coordinated reciprocal and bidirectional regulation among MEKK3, FBW7, WDR62, and JNK1, is required for fine-tuned JNK signaling for the control of balanced NPC self-renewal and differentiation during cortical development. © 2018 Xu et al. http://creativecommons.org/licenses/by/4.0/.

Keyword:

Community:

  • [ 1 ] [Xu, D.]State Key Laboratory of Molecular Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
  • [ 2 ] [Xu, D.]College of Biological Science and Engineering, Institute of Life Sciences, Fuzhou University, Fuzhou, China
  • [ 3 ] [Yao, M.]State Key Laboratory of Molecular Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
  • [ 4 ] [Wang, Y.]State Key Laboratory of Molecular Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
  • [ 5 ] [Yuan, L.]Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China
  • [ 6 ] [Hoeck, J.D.]CR-UK London Research Institute, London, United Kingdom
  • [ 7 ] [Yu, J.]State Key Laboratory of Molecular Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
  • [ 8 ] [Liu, L.]State Key Laboratory of Molecular Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
  • [ 9 ] [Yeap, Y.Y.C.]School of Biomedical Science, Faculty of Medicine, University of Queensland, St Lucia, Australia
  • [ 10 ] [Zhang, W.]State Key Laboratory of Molecular Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
  • [ 11 ] [Zhang, F.]State Key Laboratory of Molecular Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
  • [ 12 ] [Feng, Y.]Sino-Danish College, University of Chinese Academy of Science, Beijing, China
  • [ 13 ] [Ma, T.]State Key Laboratory of Molecular Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
  • [ 14 ] [Wang, Y.]College of Biological Science and Engineering, Institute of Life Sciences, Fuzhou University, Fuzhou, China
  • [ 15 ] [Ng, D.C.H.]School of Biomedical Science, Faculty of Medicine, University of Queensland, St Lucia, Australia
  • [ 16 ] [Niu, X.]Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • [ 17 ] [Su, B.]Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • [ 18 ] [Su, B.]Department of Immunobiology, Yale University School of Medicine, New Haven, CT, United States
  • [ 19 ] [Behrens, A.]Adult Stem Cell Laboratory, The Francis Crick Institute, London, United Kingdom
  • [ 20 ] [Behrens, A.]King’s College London, Faculty of Life Sciences and Medicine, Guy’s Campus, London, United Kingdom
  • [ 21 ] [Xu, Z.]State Key Laboratory of Molecular Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
  • [ 22 ] [Xu, Z.]Sino-Danish College, University of Chinese Academy of Science, Beijing, China
  • [ 23 ] [Xu, Z.]Parkinson’s Disease Center, Beijing Institute for Brain Disorders, Beijing, China

Reprint 's Address:

  • [Xu, Z.]State Key Laboratory of Molecular Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Genetics and Developmental Biology, Chinese Academy of SciencesChina

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Source :

PLoS Biology

ISSN: 1544-9173

Year: 2018

Issue: 12

Volume: 16

8 . 3 8 6

JCR@2018

7 . 8 0 0

JCR@2023

ESI HC Threshold:212

JCR Journal Grade:1

CAS Journal Grade:1

Cited Count:

WoS CC Cited Count:

SCOPUS Cited Count: 12

ESI Highly Cited Papers on the List: 0 Unfold All

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 2

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