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

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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.

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Acknowledgements

DN acknowledges funding support from the National Health and Medical Research Council (APP1046032), Australian Research Council (FT120100193) and Cancer Council (APP1101931). NL was a recipient of a Melbourne International Research Scholarship from the University of Melbourne and BS is a recipient of a UQ International Scholarship from the University of Queensland.

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  1. Nicholas Rui Lim

    Present address: Duke-NUS Medical School, Singapore, Singapore

Authors and Affiliations

  1. School of Biomedical Sciences, Faculty of Medicine, University of Queensland, St Lucia, QLD, Australia

    Belal Shohayeb, Uda Ho & Dominic Chi Hiung Ng

  2. Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC, Australia

    Nicholas Rui Lim

  3. State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China

    Zhiheng Xu

  4. Centre for Neural Engineering, The University of Melbourne, Carlton, VIC, 3010, Australia

    Mirella Dottori

  5. Department of Cancer Biology and Therapeutics, John Curtin School of Medical Research, Australian National University, Canberra, Australia

    Leonie Quinn

Authors
  1. Belal Shohayeb
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  2. Nicholas Rui Lim
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  3. Uda Ho
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  4. Zhiheng Xu
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  5. Mirella Dottori
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  6. Leonie Quinn
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  7. Dominic Chi Hiung Ng
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Corresponding author

Correspondence to Dominic Chi Hiung Ng.

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Shohayeb, B., Lim, N.R., Ho, U. et al. The Role of WD40-Repeat Protein 62 (MCPH2) in Brain Growth: Diverse Molecular and Cellular Mechanisms Required for Cortical Development. Mol Neurobiol 55, 5409–5424 (2018). https://doi.org/10.1007/s12035-017-0778-x

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  • DOI: https://doi.org/10.1007/s12035-017-0778-x

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