Drosophila Blimp-1 Is a Transient Transcriptional Repressor That Controls Timing of the Ecdysone-Induced Developmental Pathway▿

Regulatory mechanisms controlling the timing of developmental events are crucial for proper development to occur. ftz-f1 is expressed in a temporally regulated manner following pulses of ecdysteroid and this precise expression is necessary for the development of Drosophila melanogaster. To understand how insect hormone ecdysteroids regulate the timing of FTZ-F1 expression, we purified a DNA binding regulator of ftz-f1. Mass spectroscopy analysis revealed this protein to be a fly homolog of mammalian B lymphocyte-induced maturation protein 1 (Blimp-1). Drosophila Blimp-1 (dBlimp-1) is induced directly by 20-hydroxyecdysone, and its product exists during high-ecdysteroid periods and turns over rapidly. Forced expression of dBlimp-1 and RNA interference analysis indicate that dBlimp-1 acts as a repressor and controls the timing of FTZ-F1 expression. Furthermore, its prolonged expression results in delay of pupation timing. These results suggest that the transient transcriptional repressor dBlimp-1 is important for determining developmental timing in the ecdysone-induced pathway

Table S2. Results from the high-content screen. from An <i>in vivo</i> genetic screen in <i>Drosophila</i> identifies the orthologue of human cancer/testis gene <i>SPO11</i> among a network of targets to inhibit <i>lethal(3)malignant brain tumour</i> growth

The table contains all the information regarding the high-content screen including the list of all the RNAi lines screened, the corresponding VDRC UAS-RNAi line ID, FlyBase ID, CG name, Symbol, and the behaviour in the screen assay. Lines that performed as mbt tumor suppressors only in the first in both first and second rounds of screen are labeled orange and green, respectively. Only the latter (green) were tagged as confirmed mbt-SPRs. Lines that lead to larval lethality or larval brains smaller than wild type are labeled brown and purple, respectively

Supplemental Figures and figure legends 1 to 6 from An <i>in vivo</i> genetic screen in <i>Drosophila</i> identifies the orthologue of human cancer/testis gene <i>SPO11</i> among a network of targets to inhibit <i>lethal(3)malignant brain tumour</i> growth

Using transgenic RNAi technology, we have screened over 4.000 genes to identify targets to inhibit malignant growth caused by the loss of function of <i>lethal(3)malignant brain tumour</i> (mbt) in <i>Drosophila in vivo</i>. We have identified 131 targets, which belong to a wide range of gene ontologies. Most of these target genes are not significantly overexpressed in mbt tumours hence showing that, rather counterintuitively, tumour-linked overexpression is not a good predictor of functional requirement. Moreover, we have found that most of the genes upregulated in mbt tumours remain overexpressed in tumour-suppressed double-mutant conditions, hence revealing that most of the tumour transcriptome signature is not necessarily correlated with malignant growth. One of the identified target genes is <i>meiotic W68</i> (<i>mei-W68</i>), the <i>Drosophila</i> orthologue of the human Cancer Testes gene <i>Sporulation-specific protein 11</i> (<i>SPO11</i>), the enzyme that catalyses the formation of meiotic double-strand breaks. We show that <i>Drosophila mei-W68/SPO11</i> drives oncogenesis by causing DNA damage in a somatic tissue, hence providing the first instance in which a <i>SPO11</i> orthologue is unequivocally shown to have a pro-tumoural role. Altogether, the results from this screen point to the possibility of investigating the function of human cancer relevant genes in a tractable experimental model organism like <i>Drosophila.</i