Abstract:
:Genetic disruptions of spindle/centrosome-associated WD40-repeat protein 62 (WDR62) are causative for autosomal recessive primary microcephaly (MCPH) and a broader range of cortical malformations. Since the identification of WDR62 as encoded by the MCPH2 locus in 2010, recent studies that have deleted/depleted WDR62 in various animal models of cortical development have highlighted conserved functions in brain growth. Here, we provide a timely review of our current understanding of WDR62 contributions in the self-renewal, expansion and fate specification of neural stem and progenitor cells that are critical for neocortical development. Recent studies have revealed multiple functions for WDR62 in the regulation of spindle organization, mitotic progression and the duplication and biased inheritance of centrosomes during asymmetric divisions. We also discuss recently elaborated WDR62 interaction partners that include Aurora and c-Jun N-terminal kinases as part of complex signalling mechanisms that may define its neural functions. These studies provide new insights into the molecular and cellular processes that are required for brain formation and implicated in the genesis of primary microcephaly.
journal_name
Mol Neurobioljournal_title
Molecular neurobiologyauthors
Shohayeb B,Lim NR,Ho U,Xu Z,Dottori M,Quinn L,Ng DCHdoi
10.1007/s12035-017-0778-xsubject
Has Abstractpub_date
2018-07-01 00:00:00pages
5409-5424issue
7eissn
0893-7648issn
1559-1182pii
10.1007/s12035-017-0778-xjournal_volume
55pub_type
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