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

Biochim Biophys Acta Mol Cell Res. 2020 Jul;1867(7):118713. doi: 10.1016/j.bbamcr.2020.118713. Epub 2020 Apr 1.

Abstract

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.

Keywords: Cell growth; Cell proliferation; Glia; MYC; Signal transduction; WD40 domains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aurora Kinase A / genetics*
  • Brain / growth & development
  • Brain / metabolism
  • Cell Proliferation / genetics
  • DNA-Binding Proteins / genetics*
  • Drosophila / genetics
  • Drosophila / growth & development
  • Drosophila Proteins / genetics*
  • Nerve Tissue Proteins / genetics*
  • Neurogenesis / genetics
  • Neuroglia / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Signal Transduction / genetics
  • Spindle Apparatus / genetics
  • Transcription Factors / genetics*

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Myc protein, Drosophila
  • Nerve Tissue Proteins
  • Transcription Factors
  • Wdr62 protein, Drosophila
  • Aurora Kinase A
  • Proto-Oncogene Proteins c-akt