Transcriptional signature of an adult brain tumor in Drosophila

Loop, Thomas; Leemans, Ronny; Stiefel, Urs; Hermida, Leandro; Egger, Boris; Xie, Fukang; Primig, Michael; Certa, Ulrich; Fischbach, Karl‐Friedrich; Reichert, Heinrich; Hirth, Frank

doi:10.1186/1471-2164-5-24

Cited by 34 publications

(15 citation statements)

References 88 publications

(97 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with our hypothesis, mRNA levels of four genes expressed in Type I and Type II neural progenitors: asense ( ase ), deadpan ( dpn ), miranda ( mira ) and klumpfuss ( klu ), were all upregulated in heads from hemizygous brat chs /Df(2L)ED1272 flies, compared with heads from brat chs /+ controls ( Figure 6B ). These data are consistent with a previous study that found an increase in dpn , mira and klu mRNA in another brat mutant ( Loop et al 2004 ). We also found an increase in pointed P1 mRNA levels in brat chs /Df(2L)ED1272 flies ( Figure 6B ), which specifically implicates involvement of the Type II lineage.…”

Section: Resultssupporting

confidence: 94%

“…, brat k06028 , brat ts1 and brat fs1 ) ( Arama et al 2000 ). An adult brain overgrowth phenotype had been observed in homozygous brat k06028 mutants carrying a transposable element inserted into a non-coding region of the brat locus ( Loop et al 2004 ). However, we were unable to obtain viable adults even at low temperatures (18°) from any of the abovementioned lines and therefore couldn’t assess their neurodegenerative phenotypes.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A Novel Mutation in Brain Tumor Causes Both Neural Over-Proliferation and Neurodegeneration in AdultDrosophila

Loewen

Boekhoff-Falk

Ganetzky

et al. 2018

G3 Genes|Genomes|Genetics

View full text Add to dashboard Cite

A screen for neuroprotective genes in Drosophila melanogaster led to the identification of a mutation that causes extreme, progressive loss of adult brain neuropil in conjunction with massive brain overgrowth. We mapped the mutation to the brain tumor (brat) locus, which encodes a tripartite motif-NCL-1, HT2A, and LIN-41 (TRIM-NHL) RNA-binding protein with established roles limiting stem cell proliferation in developing brain and ovary. However, a neuroprotective role for brat in the adult Drosophila brain has not been described previously. The new allele, bratcheesehead (bratchs), carries a mutation in the coiled-coil domain of the TRIM motif, and is temperature-sensitive. We demonstrate that mRNA and protein levels of neural stem cell genes are increased in heads of adult bratchs mutants and that the over-proliferation phenotype initiates prior to adult eclosion. We also report that disruption of an uncharacterized gene coding for a presumptive prolyl-4-hydroxylase strongly enhances the over-proliferation and neurodegeneration phenotypes. Together, our results reveal an unexpected role for brat that could be relevant to human cancer and neurodegenerative diseases.

show abstract

Section: Resultssupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

A Novel Mutation in Brain Tumor Causes Both Neural Over-Proliferation and Neurodegeneration in AdultDrosophila

Loewen

Boekhoff-Falk

Ganetzky

et al. 2018

G3 Genes|Genomes|Genetics

View full text Add to dashboard Cite

show abstract

“…We examined roles for brat during metamorphosis because, unlike the other six 20E primary-response genes described above, a brat mutant allele is available ( brat k06028 ) that allows an assessment of its functions during later stages of development [ 25 , 50 ]. The brat k06028 P -element maps to the fourth exon of the brat gene.…”

Section: Resultsmentioning

confidence: 99%

Untitled

2005

View full text Add to dashboard Cite

Background: The steroid hormone 20-hydroxyecdysone (20E) triggers the major developmental transitions in Drosophila, including molting and metamorphosis, and provides a model system for defining the developmental and molecular mechanisms of steroid signaling. 20E acts via a heterodimer of two nuclear receptors, the ecdysone receptor (EcR) and Ultraspiracle, to directly regulate target gene transcription.

show abstract

“…Genomewide microarray analysis of Drosophila brain tumor caused by the disfunction of the Brat tumor suppressor gene has identified over three hundred associated genes. Sixty of these sequences show homology to existing mammalian genes involved in tumor development [31]. As in human cancers, loss of heterozygosity can lead to tumor formation as reported in the case of the warts ( wts ) sequence.…”

Section: Senescence Cancer and Immunosuppressive Virusesmentioning

confidence: 99%

Blurring Borders: Innate Immunity with Adaptive Features

Kvell

Engelmann

et al. 2007

Clinical and Developmental Immunology

View full text Add to dashboard Cite

Adaptive immunity has often been considered the penultimate of immune capacities. That system is now being deconstructed to encompass less stringent rules that govern its initiation, actual effector activity, and ambivalent results. Expanding the repertoire of innate immunity found in all invertebrates has greatly facilitated the relaxation of convictions concerning what actually constitutes innate and adaptive immunity. Two animal models, incidentally not on the line of chordate evolution (C. elegans and Drosophila), have contributed enormously to defining homology. The characteristics of specificity and memory and whether the antigen is pathogenic or nonpathogenic reveal considerable information on homology, thus deconstructing the more fundamentalist view. Senescence, cancer, and immunosuppression often associated with mammals that possess both innate and adaptive immunity also exist in invertebrates that only possess innate immunity. Strict definitions become blurred casting skepticism on the utility of creating rigid definitions of what innate and adaptive immunity are without considering overlaps.

show abstract

Transcriptional signature of an adult brain tumor in Drosophila

Cited by 34 publications

References 88 publications

A Novel Mutation in Brain Tumor Causes Both Neural Over-Proliferation and Neurodegeneration in AdultDrosophila

A Novel Mutation in Brain Tumor Causes Both Neural Over-Proliferation and Neurodegeneration in AdultDrosophila

Untitled

Blurring Borders: Innate Immunity with Adaptive Features

Contact Info

Product

Resources

About