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author:

Xu, D. (Xu, D..) [1] | Zhi, Y. (Zhi, Y..) [2] | Liu, X. (Liu, X..) [3] | Guan, L. (Guan, L..) [4] | Yu, J. (Yu, J..) [5] | Zhang, D. (Zhang, D..) [6] | Zhang, W. (Zhang, W..) [7] | Wang, Y. (Wang, Y..) [8] | Tao, W. (Tao, W..) [9] | Xu, Z. (Xu, Z..) [10]

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Scopus CSCD

Abstract:

Brain size abnormality is correlated with an increased frequency of autism spectrum disorder (ASD) in offspring. Genetic analysis indicates that heterozygous mutations of the WD repeat domain 62 (WDR62) are associated with ASD. However, biological evidence is still lacking. Our study showed that Wdr62 knockout (KO) led to reduced brain size with impaired learning and memory, as well as ASD-like behaviors in mice. Interestingly, Wdr62 Nex-cKO mice (depletion of WDR62 in differentiated neurons) had a largely normal brain size but with aberrant social interactions and repetitive behaviors. WDR62 regulated dendritic spinogenesis and excitatory synaptic transmission in cortical pyramidal neurons. Finally, we revealed that retinoic acid gavages significantly alleviated ASD-like behaviors in mice with WDR62 haploinsufficiency, probably by complementing the expression of ASD and synapse-related genes. Our findings provide a new perspective on the relationship between the microcephaly gene WDR62 and ASD etiology that will benefit clinical diagnosis and intervention of ASD. © 2022, The Author(s).

Keyword:

Autism spectrum disorder Microcephaly Retinoic acid Synapse WDR62

Community:

  • [ 1 ] [Xu D.]Fujian Key Laboratory of Molecular Neurology, Institute of Neuroscience, Fujian Medical University, Fuzhou, 350005, China
  • [ 2 ] [Zhi Y.]College of Biological Science and Engineering, Institute of Life Sciences, Fuzhou University, Fuzhou, 350108, China
  • [ 3 ] [Liu X.]University of Chinese Academy of Sciences, Beijing, 100101, China
  • [ 4 ] [Liu X.]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, 100101, China
  • [ 5 ] [Guan L.]Key Laboratory of Brain Aging and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350108, China
  • [ 6 ] [Yu J.]College of Biological Science and Engineering, Institute of Life Sciences, Fuzhou University, Fuzhou, 350108, China
  • [ 7 ] [Zhang D.]University of Chinese Academy of Sciences, Beijing, 100101, China
  • [ 8 ] [Zhang 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, 100101, China
  • [ 9 ] [Zhang W.]University of Chinese Academy of Sciences, Beijing, 100101, China
  • [ 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, 100101, China
  • [ 11 ] [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, 100101, China
  • [ 12 ] [Tao W.]Key Laboratory of Brain Aging and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350108, China
  • [ 13 ] [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, 100101, China

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Source :

Neuroscience Bulletin

ISSN: 1673-7067

Year: 2023

Issue: 9

Volume: 39

Page: 1333-1347

5 . 9

JCR@2023

5 . 9 0 0

JCR@2023

JCR Journal Grade:1

CAS Journal Grade:3

Cited Count:

WoS CC Cited Count:

SCOPUS Cited Count:

ESI Highly Cited Papers on the List: 0 Unfold All

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 5

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