Reference Report

Reference
Citation	Richter, C., Oktaba, K., Steinmann, J., Müller, J., Knoblich, J.A. (2011). The tumour suppressor L(3)mbt inhibits neuroepithelial proliferation and acts on insulator elements. Nat. Cell Biol. 13(9): 1029--1039. (Export to RIS)
FlyBase ID	FBrf0215050
Publication Type	Research paper
PubMed ID	21857667
PubMed Abstract	In Drosophila, defects in asymmetric cell division often result in the formation of stem-cell-derived tumours. Here, we show that very similar terminal brain tumour phenotypes arise through a fundamentally different mechanism. We demonstrate that brain tumours in l(3)mbt mutants originate from overproliferation of neuroepithelial cells in the optic lobes caused by derepression of target genes in the Salvador-Warts-Hippo (SWH) pathway. We use ChIP-sequencing to identify L(3)mbt binding sites and show that L(3)mbt binds to chromatin insulator elements. Mutating l(3)mbt or inhibiting expression of the insulator protein gene mod(mdg4) results in upregulation of SWH pathway reporters. As l(3)mbt tumours are rescued by mutations in bantam or yorkie or by overexpression of Expanded, the deregulation of SWH pathway target genes is an essential step in brain tumour formation. Therefore, very different primary defects result in the formation of brain tumours, which behave quite similarly in their advanced stages.
DOI	10.1038/ncb2306
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Nat. Cell Biol.
Title	Nature Cell Biology
Publication Year	1999-
ISBN/ISSN	1465-7392 1476-4679
Data from Reference
Aberrations (2)
	Df(3L)ban^Δ1 Df(3R)D605
Alleles (25)
	Avic\GFP^{EGFP.ban.αTub84B} Avic\GFP^Stat92E.10X Avic\GFP^{th.4.3.T:nls-tra} Avic\GFP^{th.5.1.T:nls-tra} BacA\p35^Scer\UAS.cHa ban^{D.Scer\UAS.T:Avic\GFP-EGFP} bsk^{K53R.Scer\UAS} btl::Egfr^{Scer\UAS.T:λ\cI-DD} Ecol\lacZ^ex-697 ex^Scer\UAS.cBa hop^Tum.Scer\UAS hpo^Scer\UAS.cUa htl^{Scer\UAS.T:λ\cI-DD} l(3)mbt^E2 l(3)mbt^GM76 l(3)mbt^{miRNA.Scer\UAS} l(3)mbt^{Scer\UAS.T:Avic\GFP} l(3)mbt^{Scer\UAS.T:Disc\RFP} l(3)mbt^ts1 mod(mdg4)^GD16547 Scer\GAL4^C855a Scer\GAL4^en.PU Scer\GAL4^insc-Mz1407 yki^B5 yki^{S168A.Scer\UAS.T:Disc\RFP}
Constructs (13)
	P{10XStat92E-GFP} P{GD16547} P{th-GFP.4.3} P{th-GFP.5.1} P{Tub-EGFP.ban} P{UAS-bsk.K53R} P{UAS-Egfr.λtop} P{UAS-GFP-l(3)mbt} P{UAS-hop.Tum} P{UAS-htl.λ\cI.M} P{UAS-l(3)mbt.miRNA} P{UAS-RFP-l(3)mbt} P{UAS-yki.S168A.RFP}
Genes (45)
	Abd-B aPKC Avic\GFP BacA\p35 bam ban BEAF-32 bgcn bsk btl::Egfr cnn Cp190 CTCF CycA CycB CycE dpn E2f Ecol\lacZ ex fj hop hpo htl l(3)mbt Mer mira mod(mdg4) ph-d pho ph-p pros Scer\GAL4 sd Ser Sfmbt shg su(Hw) T:Avic\GFP T:Disc\RFP th Ubx vas wg yki
Insertions (1)
	P{lacW}ex⁶⁹⁷
Natural transposons (1)
	P-element