The Role of WD40-Repeat Protein 62 (MCPH2) in Brain Growth: Diverse Molecular and Cellular Mechanisms Required for Cortical Development

Belal Shohayeb, Nicholas Rui Lim, Uda Ho, Zhiheng Xu, Mirella Dottori, Leonie Quinn, Dominic Chi Hiung Ng*

*Corresponding author for this work

    Research output: Contribution to journalReview articlepeer-review

    19 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)5409-5424
    Number of pages16
    JournalMolecular Neurobiology
    Volume55
    Issue number7
    DOIs
    Publication statusPublished - 1 Jul 2018

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