Stem Cell Reports
Volume 9, Issue 1, 11 July 2017, Pages 32-41
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Glial-Specific Functions of Microcephaly Protein WDR62 and Interaction with the Mitotic Kinase AURKA Are Essential for Drosophila Brain Growth

https://doi.org/10.1016/j.stemcr.2017.05.015Get rights and content
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Highlights

  • Glial-specific depletion of microcephaly protein WDR62 impairs brain growth

  • wdr62 depletion in glia causes neural stem cell (NSC) loss

  • WDR62 is required cell extrinsically in the NSC niche

  • Lineage-specific interactions between WDR62 and AURKA control brain growth

Summary

The second most commonly mutated gene in primary microcephaly (MCPH) patients is wd40-repeat protein 62 (wdr62), but the relative contribution of WDR62 function to the growth of major brain lineages is unknown. Here, we use Drosophila models to dissect lineage-specific WDR62 function(s). Interestingly, although neural stem cell (neuroblast)-specific depletion of WDR62 significantly decreased neuroblast number, brain size was unchanged. In contrast, glial lineage-specific WDR62 depletion significantly decreased brain volume. Moreover, loss of function in glia not only decreased the glial population but also non-autonomously caused neuroblast loss. We further demonstrated that WDR62 controls brain growth through lineage-specific interactions with master mitotic signaling kinase, AURKA. Depletion of AURKA in neuroblasts drives brain overgrowth, which was suppressed by WDR62 co-depletion. In contrast, glial-specific depletion of AURKA significantly decreased brain volume, which was further decreased by WDR62 co-depletion. Thus, dissecting relative contributions of MCPH factors to individual neural lineages will be critical for understanding complex diseases such as microcephaly.

Keywords

neuroblast
glia
WD-repeat protein
WDR62
AURKA
mitosis
Drosophila
brain
microcephaly

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4

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5

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