Reference Report

Reference
Citation	Wang, C., Chang, K.C., Somers, G., Virshup, D., Ang, B.T., Tang, C., Yu, F., Wang, H. (2009). Protein phosphatase 2A regulates self-renewal of Drosophila neural stem cells. Development 136(13): 2287--2296. (Export to RIS)
FlyBase ID	FBrf0208148
Publication Type	Research paper
PubMed ID	19502489
PubMed Abstract	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 primarily by regulating asymmetric localization and activation of Numb. Reduction of PP2A function in larval brains or S2 cells causes a marked decrease in Polo transcript and protein abundance. Overexpression of Polo or Numb significantly suppresses neuroblast overgrowth in PP2A mutants, suggesting that PP2A inhibits excess neuroblast self-renewal in the Polo/Numb pathway.
DOI	10.1242/dev.035758
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Development
Title	Development
Publication Year	1987-
ISBN/ISSN	0950-1991
Data from Reference
Alleles (27)
	aPKC^k06403 aur^87Ac-3 aur⁸⁸³⁹ mts²⁹⁹ mts^GD12133 mts^s5286 mts^Scer\UAS.cHa mts^unspecified mts^XE-2258 numb^{PTB.Scer\UAS.T:Avic\GFP} par-1^Δ-16 polo¹¹ polo^S025604 polo^{Scer\UAS.T:Avic\GFP-YFP.Venus} polo^T:Avic\GFP Pp2A-29B^CB-5426-3 Pp2A-29B^EP2332 Pp2A-29B^GD17607 PP2A-B'^KG01108 Scer\GAL4^ase.neuro Scer\GAL4^insc-Mz1407 T:Avic\GFP^YFP.Venus tws⁶⁰ tws⁰²⁴¹⁴ wdb^12-1es wdb^dw wdb^IP
Constructs (7)
	P{ase-GAL4} P{GD12133} P{GD17607} P{GFP-polo} P{UAS-mts.H} P{UAS-numb.PTB.GFP} P{UAS-polo.Venus}
Genes (28)
	aPKC ase aur baz brat CG4733 CycE dm dpn elav His3 insc l(2)gl mira mts N numb par-1 par-6 polo pon Pp2A-29B PP2A-B' pros Scer\GAL4 tws wdb wor
Insertions (1)
	P{GawB}insc^Mz1407