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author:

Zhi, Yiqiang (Zhi, Yiqiang.) [1] | Yu, Jurui (Yu, Jurui.) [2] | Zhong, Yilin (Zhong, Yilin.) [3] | Fu, Honggao (Fu, Honggao.) [4] | Zhou, Xiaokun (Zhou, Xiaokun.) [5] | Yi, Wenxiang (Yi, Wenxiang.) [6] | Yuan, Ling (Yuan, Ling.) [7] | Xu, Zhiheng (Xu, Zhiheng.) [8] | Xu, Dan (Xu, Dan.) [9]

Indexed by:

Scopus SCIE

Abstract:

WD repeat domain 62 (WDR62) was identified as the second most causative gene of autosomal recessive primary microcephaly (MCPH) frequently associated structural abnormalities such as lissencephaly, polymicrogyria as well as hypoplasia of the corpus callosum, however, underlining mechanism behind these abnormality remains unknown. Here we show that either ablation of WDR62 in neural progenitor cells (NPCs) or post-mitotic neurons both impedes cortical neuronal radial migration in the developing brain. WDR62 modulates the transition from multipolar to bipolar states in migrating neurons and ensures the accurate formation of contralateral projections of callosal neurons. Our results further indicated that ASD-related mutations in WDR62 are associated with a reduced capacity for neuronal migration in the developing brain. Finally, we provide the molecular evidence that the levels of Reelin, a key modulator of neuronal migration and high confidence ASD candidate gene, were significantly reduced in the brains of Wdr62 deficient mice. These finding define critical roles for WDR62 in cortical neuronal radial migration and callosal projection which provides insights into the pathogenesis of WDR62 deficiency-related brain dysplasia.

Keyword:

ASD Callosal projection Radial migration RELN WDR62

Community:

  • [ 1 ] [Zhi, Yiqiang]Fujian Med Univ, Sch Basic Med Sci, Inst Neurosci, Fujian Key Lab Mol Neurol, Fuzhou 350005, Peoples R China
  • [ 2 ] [Zhong, Yilin]Fujian Med Univ, Sch Basic Med Sci, Inst Neurosci, Fujian Key Lab Mol Neurol, Fuzhou 350005, Peoples R China
  • [ 3 ] [Fu, Honggao]Fujian Med Univ, Sch Basic Med Sci, Inst Neurosci, Fujian Key Lab Mol Neurol, Fuzhou 350005, Peoples R China
  • [ 4 ] [Yi, Wenxiang]Fujian Med Univ, Sch Basic Med Sci, Inst Neurosci, Fujian Key Lab Mol Neurol, Fuzhou 350005, Peoples R China
  • [ 5 ] [Xu, Dan]Fujian Med Univ, Sch Basic Med Sci, Inst Neurosci, Fujian Key Lab Mol Neurol, Fuzhou 350005, Peoples R China
  • [ 6 ] [Yu, Jurui]Fuzhou Univ, Inst Life Sci, Coll Biol Sci & Engn, Fuzhou 350108, Peoples R China
  • [ 7 ] [Zhou, Xiaokun]Fuzhou Univ, Inst Life Sci, Coll Biol Sci & Engn, Fuzhou 350108, Peoples R China
  • [ 8 ] [Yuan, Ling]Cent South Univ, Ctr Med Genet, Sch Life Sci, Changsha 410028, Peoples R China
  • [ 9 ] [Xu, Zhiheng]Chinese Acad Sci, Inst Genet & Dev Biol, CAS Ctr Excellence Brain Sci & Intelligence Techno, State Key Lab Mol Dev Biol, Beijing 100101, Peoples R China

Reprint 's Address:

  • [Xu, Dan]Fujian Med Univ, Sch Basic Med Sci, Inst Neurosci, Fujian Key Lab Mol Neurol, Fuzhou 350005, Peoples R China;;[Xu, Zhiheng]Chinese Acad Sci, Inst Genet & Dev Biol, CAS Ctr Excellence Brain Sci & Intelligence Techno, State Key Lab Mol Dev Biol, Beijing 100101, Peoples R China

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Source :

NEUROBIOLOGY OF DISEASE

ISSN: 0969-9961

Year: 2025

Volume: 211

5 . 1 0 0

JCR@2023

CAS Journal Grade:2

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: 3

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