RRC ID 48860
Author Lim NR, Shohayeb B, Zaytseva O, Mitchell N, Millard SS, Ng DCH, Quinn LM.
Title Glial-Specific Functions of Microcephaly Protein WDR62 and Interaction with the Mitotic Kinase AURKA Are Essential for Drosophila Brain Growth.
Journal Stem Cell Reports
Abstract 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.
Volume 9(1)
Pages 32-41
Published 2017-7-11
DOI 10.1016/j.stemcr.2017.05.015
PII S2213-6711(17)30222-9
PMID 28625535
PMC PMC5511370
MeSH Animals Aurora Kinase A / genetics Aurora Kinase A / metabolism* Brain / growth & development* Brain / metabolism Drosophila / genetics Drosophila / growth & development* Drosophila / metabolism Drosophila Proteins / genetics Drosophila Proteins / metabolism* Gene Knockdown Techniques Mitosis Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism* Neuroglia / cytology Neuroglia / metabolism* Protein Interaction Maps*
IF 6.032
Times Cited 15
WOS Category CELL & TISSUE ENGINEERING CELL BIOLOGY
Resource
Drosophila 7337-R1