Protein phosphatase 2A regulates self-renewal of Drosophila neural stem cells
K. C Chang,
B. T Ang,
2009, 136(13), 2287-2296. DOI: 10.1242/dev.035758
Cheng Wang, Kai Chen Chang, Gregory Somers, David Virshup, Beng Ti Ang, Carol Tang, Fengwei Yu, and Hongyan Wang
Drosophila larval brain neural stem cells, also known as
neuroblasts, divide asymmetrically to generate a self-renewing neuroblast and
a ganglion mother cell (GMC) that divides terminally to produce two
differentiated neurons or glia. Failure of asymmetric cell division can result
in hyperproliferation of neuroblasts, a phenotype resembling brain tumors.
Here we have identified Drosophila Protein phosphatase 2A (PP2A) as a
brain tumor-suppressor that can inhibit self-renewal of neuroblasts.
Supernumerary larval brain neuroblasts are generated at the expense of
differentiated neurons in PP2A mutants. Neuroblast overgrowth was
observed in both dorsomedial (DM)/posterior Asense-negative (PAN) neuroblast
lineages and non-DM neuroblast lineages. The PP2A heterotrimeric complex,
composed of the catalytic subunit (Mts), scaffold subunit (PP2A-29B) and a
B-regulatory subunit (Tws), is required for the asymmetric cell division of
neuroblasts. The PP2A complex regulates asymmetric localization of Numb, Pon
and Atypical protein kinase C, as well as proper mitotic spindle orientation.
Interestingly, PP2A and Polo kinase enhance Numb and Pon phosphorylation.
PP2A, like Polo, acts to prevent excess neuroblast self-renewal...