Developmental expression of drop-dead is required for early adult survival and normal body mass in Drosophila melanogaster

Sansone, Christine Lynn; Blumenthal, Edward M.

doi:10.1016/j.ibmb.2012.06.002

Cited by 6 publications

(15 citation statements)

References 51 publications

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“…We have previously demonstrated that targeted knockdown and rescue of drd expression can recapitulate and rescue, respectively, early adult lethality [8]. We utilized this system to determine the tissues necessary for the neurodegenerative phenotype observed in drd mutants.…”

Section: Resultsmentioning

confidence: 99%

“…RNAi experiments used the 51184 UAS-Dcr-2 and UAS-Dcr-2 37404 lines created previously by recombination between VDRC stocks w 1118 ;P{GD3367}v37404 (FBst0461992) and w 1118 ; P{GD15915}v51184 (FBst0469325) and Bloomington stock w 1118 ; P{UAS-Dcr-2.D}2 (FBst0024650) [8]. Other stocks ( w 1118 ; P{GAL4}repo/TM3, Sb 1 (FBst0007415), w * ; P{GawB}17A/CyO (FBst0008474), w * ; P{GAL4-btl.S}2, P{UASp-Act5C.T:GFP}2/CyO, P{lacZ-un8}276 (FBst0008807, referred to as btl-Gal4(II) ), y 1 w * ; P{Act5CGAL4}17bFO1/TM6B, Tb 1 (FBst0003954), w * ; P{UAS-lacZ.B}Bg4-2-4b(FBst0001777), w 1118 ; P{GawB}DJ717 (FBst0008180), and y 1 w * ; wg Sp-1 /CyO; P{btl-moe.mRFP1}3, P{GAL4-btl.S}3-1, P{UAS-mCD8::GFP.L}LL6/TM6B, Tb 1 (FBst0041803, referred to as btl-Gal4(III) )) were obtained from the Bloomington Drosophila Stock Center.…”

Section: Methodsmentioning

confidence: 99%

“…The LDH-LacZ and LDH-Gal4 UAS-GFP lines were gifts from Pablo Wappner and Jon Harrison. The line bearing the UAS-drd on the second chromosome on a drd lwf background was described previously [8]. The genes and alleles referenced in this work include drd (FBgn0260006), drd lwf (FBal0193421), similar (FBgn0015542), tango (FBgn0264075), lactate dehydrogenase (FBgn0001258), and rp49 (FBgn0002626).…”

Section: Methodsmentioning

confidence: 99%

“…For survival, drd expression is both necessary and sufficient during mid to late metamorphosis, indicating that drd is an essential developmental gene. In contrast, the attainment of normal adult body mass requires drd expression during a broader period of development [8].…”

Section: Introductionmentioning

confidence: 99%

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Neurodegeneration in Drop-Dead Mutant Drosophila melanogaster Is Associated with the Respiratory System but Not with Hypoxia

Sansone

Blumenthal

2013

PLoS ONE

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Mutations in the gene drop-dead (drd) cause diverse phenotypes in adult Drosophila melanogaster including early lethality, neurodegeneration, tracheal defects, gut dysfunction, reduced body mass, and female sterility. Despite the identification of the drd gene itself, the causes of early lethality and neurodegeneration in the mutant flies remain unknown. To determine the pattern of drd expression associated with the neurodegenerative phenotype, knockdown of drd with various Gal4 drivers was performed. Early adult lethality and neurodegeneration were observed upon knockdown of drd in the tracheal system with two independent insertions of the breathless-Gal4 driver and upon knockdown in the tracheal system and elsewhere with the DJ717-Gal4 driver. Surprisingly, rescue of drd expression exclusively in the tracheae in otherwise mutant flies rescued the neurodegenerative phenotype but not adult lethality. Gut dysfunction, as measured by defecation rate, was not rescued in these flies, and gut function appeared normal upon tracheal-specific knockdown of drd. Finally, the hypothesis that tracheal dysfunction in drd mutants results in hypoxia was tested. Hypoxia-sensitive reporter transgenes (LDH-Gal4 and LDH-LacZ) were placed on a drd mutant background, but enhanced expression of these reporters was not observed. In addition, manipulation of drd expression in the tracheae did not affect expression of the hypoxia-induced genes LDH, tango, and similar. Overall, these results indicate that there are at least two causes of adult lethality in drd mutants, that gut dysfunction and neurodegeneration are independent phenotypes, and that neurodegeneration is associated with tracheal expression of drd but not with hypoxia.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neurodegeneration in Drop-Dead Mutant Drosophila melanogaster Is Associated with the Respiratory System but Not with Hypoxia

Sansone

Blumenthal

2013

PLoS ONE

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“…drd mutant flies also exhibit widespread neurodegeneration in the brain, suggesting that the crop expansion results from the defective opening of the stomodeal valve, which controls entry into the midgut (35). Whatever the exact mechanism, drd mutant flies have significantly reduced levels of triglycerides and glycogen stores, like DCV-infected flies, and malnutrition has been proposed to contribute to their premature death (53,54). An alternative cause of death is the production or accumulation of toxic compounds.…”

Section: Discussionmentioning

confidence: 99%

Drosophila C Virus Systemic Infection Leads to Intestinal Obstruction

Chtarbanova

Lamiable

Lee

et al. 2014

J Virol

104

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Drosophila C virus (DCV) is a positive-sense RNA virus belonging to the Dicistroviridae family. This natural pathogen of the model organism Drosophila melanogaster is commonly used to investigate antiviral host defense in flies, which involves both RNA interference and inducible responses. Although lethality is used routinely as a readout for the efficiency of the antiviral immune response in these studies, virus-induced pathologies in flies still are poorly understood. Here, we characterize the pathogenesis associated with systemic DCV infection. Comparison of the transcriptome of flies infected with DCV or two other positive-sense RNA viruses, Flock House virus and Sindbis virus, reveals that DCV infection, unlike those of the other two viruses, represses the expression of a large number of genes. Several of these genes are expressed specifically in the midgut and also are repressed by starvation. We show that systemic DCV infection triggers a nutritional stress in Drosophila which results from intestinal obstruction with the accumulation of peritrophic matrix at the entry of the midgut and the accumulation of the food ingested in the crop, a blind muscular food storage organ. The related virus cricket paralysis virus (CrPV), which efficiently grows in Drosophila, does not trigger this pathology. We show that DCV, but not CrPV, infects the smooth muscles surrounding the crop, causing extensive cytopathology and strongly reducing the rate of contractions. We conclude that the pathogenesis associated with systemic DCV infection results from the tropism of the virus for an important organ within the foregut of dipteran insects, the crop. IMPORTANCEDCV is one of the few identified natural viral pathogens affecting the model organism Drosophila melanogaster. As such, it is an important virus for the deciphering of host-virus interactions in insects. We characterize here the pathogenesis associated with DCV infection in flies and show that it results from the tropism of the virus for an essential but poorly characterized organ in the digestive tract, the crop. Our results may have relevance for other members of the Dicistroviridae, some of which are pathogenic to beneficial or pest insect species.

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Pleiotropic and novel phenotypes in the Drosophila gut caused by mutation of drop-dead

Conway

Sansone

Benske

et al. 2018

Journal of Insect Physiology

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Normal gut function is vital for animal survival, and deviations from such function can contribute to malnutrition, inflammation, increased susceptibility to pathogens, diabetes, neurodegenerative diseases, and cancer. In the fruit fly Drosophila melanogaster, mutation of the gene drop-dead (drd) results in defective gut function, as measured by enlargement of the crop and reduced food movement through the gut, and drd mutation also causes the unrelated phenotypes of neurodegeneration, early adult lethality and female sterility. In the current work, adult drd mutant flies are also shown to lack the peritrophic matrix (PM), an extracellular barrier that lines the lumen of the midgut and is found in many insects including flies, mosquitos and termites. The use of a drd-gal4 construct to drive a GFP reporter in late pupae and adults revealed drd expression in the anterior cardia, which is the site of PM synthesis in Drosophila. Moreover, the ability of drd knockdown or rescue with several gal4 drivers to recapitulate or rescue the gut phenotypes (lack of a PM, reduced defecation, and reduced adult survival 10-40 days post-eclosion) was correlated to the level of expression of each driver in the anterior cardia. Surprisingly, however, knocking down drd expression only in adult flies, which has previously been shown not to affect survival, eliminated the PM without reducing defecation rate. These results demonstrate that drd mutant flies have a novel phenotype, the absence of a PM, which is functionally separable from the previously described gut dysfunction observed in these flies. As the first mutant Drosophila strain reported to lack a PM, drd mutants will be a useful tool for studying the synthesis of this structure.

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Developmental expression of drop-dead is required for early adult survival and normal body mass in Drosophila melanogaster

Cited by 6 publications

References 51 publications

Neurodegeneration in Drop-Dead Mutant Drosophila melanogaster Is Associated with the Respiratory System but Not with Hypoxia

Neurodegeneration in Drop-Dead Mutant Drosophila melanogaster Is Associated with the Respiratory System but Not with Hypoxia

Drosophila C Virus Systemic Infection Leads to Intestinal Obstruction

Pleiotropic and novel phenotypes in the Drosophila gut caused by mutation of drop-dead

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