Elevated levels of Drosophila Wdr62 promote glial cell growth and proliferation through AURKA signalling to AKT and MYC

• Published in: Biochimica et biophysica acta. Molecular cell research Vol. 1867; no. 7; p. 118713
• Main Authors: Shohayeb, Belal, Mitchell, Naomi, Millard, S. Sean, Quinn, Leonie M., Ng, Dominic C.H.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-07-2020
• Subjects: Cell growth; Cell proliferation; Glia; MYC; Signal transduction; WD40 domains; Cell proliferation; Signal transduction; Cell growth; WD40 domains; Glia; MYC
• ISSN: 0167-4889; 1879-2596
• DOI: 10.1016/j.bbamcr.2020.118713

WD40-Repeat Protein 62 (WDR62) is required to maintain neural and glial cell populations during embryonic brain growth. Although elevated expression of WDR62 is frequently associated with several tumour types, potential effects of excess WDR62 on proliferative growth remain undefined. Here, we demonstrate that glia specific overexpression of WDR62 in Drosophila larval brains resulted in increased cell size, over-proliferation and increased brain volume, without overt disruption of tissue organization. We further demonstrate WDR62 promoted over-proliferation and brain overgrowth by activating AURKA and pAKT signalling to increase MYC function in glial cells. Together these data suggest WDR62 normally functions in the glial lineage to activate oncogenic signalling networks, promoting proliferation and brain overgrowth.
•WDR62 overexpression promotes brain growth and proliferation of glia in Drosophila.•Growth promoting effects of WDR62 are mediated by Aurora A Kinase (AURKA).•WDR62/AURKA stimulates PI3K and AKT signalling to increase proliferation.•Increased WDR62 in glia upregulates MYC to promote cell growth.