Indexed by:
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:
Reprint 's Address:
Email:
Version:
Source :
NEUROBIOLOGY OF DISEASE
ISSN: 0969-9961
Year: 2025
Volume: 211
5 . 1 0 0
JCR@2023
CAS Journal Grade:2
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
Affiliated Colleges: