Aurora-A acts as a tumor suppressor and regulates self-renewal of Drosophila neuroblasts

  1. Hongyan Wang1,2,4,
  2. Gregory W. Somers1,
  3. Arash Bashirullah3,
  4. Ulrike Heberlein2,
  5. Fengwei Yu1, and
  6. William Chia1,5
  1. 1 Temasek Life Sciences Laboratory and Department of Biological Sciences, National University of Singapore, Singapore 117604;
  2. 2 Department of Anatomy, University of California, San Francisco, San Francisco, California 94158, USA;
  3. 3 University of Utah, Salt Lake City, Utah 84112, USA

Abstract

The choice of self-renewal versus differentiation is a fundamental issue in stem cell and cancer biology. Neural progenitors of the Drosophila post-embryonic brain, larval neuroblasts (NBs), divide asymmetrically in a stem cell-like fashion to generate a self-renewing NB and a Ganglion Mother Cell (GMC), which divides terminally to produce two differentiating neuronal/glial daughters. Here we show that Aurora-A (AurA) acts as a tumor suppressor by suppressing NB self-renewal and promoting neuronal differentiation. In aurA loss-of-function mutants, supernumerary NBs are produced at the expense of neurons. AurA suppresses tumor formation by asymmetrically localizing atypical protein kinase C (aPKC), an NB proliferation factor. Numb, which also acts as a tumor suppressor in larval brains, is a major downstream target of AurA and aPKC. Notch activity is up-regulated in aurA and numb larval brains, and Notch signaling is necessary and sufficient to promote NB self-renewal and suppress differentiation in larval brains. Our data suggest that AurA, aPKC, Numb, and Notch function in a pathway that involved a series of negative genetic interactions. We have identified a novel mechanism for controlling the balance between self-renewal and neuronal differentiation during the asymmetric division of Drosophila larval NBs.

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