Apoptotic activities of wild-type and Alzheimer's disease-related mutant presenilins in Drosophila melanogaster.
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Mutant human presenilins cause early-onset familial Alzheimer's disease and render cells susceptible to apoptosis in cultured cell models. We show that loss of presenilin function in Drosophila melanogaster increases levels of apoptosis in developing tissues. Moreover, overexpression of presenilin causes apoptotic and neurogenic phenotypes resembling those of Presenilin loss-of-function mutants, suggesting that presenilin exerts a dominant negative effect when expressed at high levels. In Drosophila S2 cells, Psn overexpression leads to reduced Notch receptor synthesis affecting levels of the intact approximately 300-kD precursor and its approximately 120-kD processed COOH-terminal derivatives. Presenilin-induced apoptosis is cell autonomous and can be blocked by constitutive Notch activation, suggesting that the increased cell death is due to a developmental mechanism that eliminates improperly specified cell types. We describe a genetic model in which the apoptotic activities of wild-type and mutant presenilins can be assessed, and we find that Alzheimer's disease-linked mutant presenilins are less effective at inducing apoptosis than wild-type presenilin. (+info)
The range of spalt-activating Dpp signalling is reduced in endocytosis-defective Drosophila wing discs.
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Pattern formation along the anterior-posterior (A/P) axis of the developing Drosophila wing depends on Decapentaplegic (Dpp), a member of the conserved transforming growth factor beta (TGFbeta) family of secreted proteins. Dpp is expressed in a stripe along the A/P compartment boundary of the wing imaginal disc and forms a long-range concentration gradient with morphogen-like properties which generates distinct cell fates along the A/P axis. We have monitored Dpp expression and Dpp signalling in endocytosis-mutant wing imaginal discs which develop severe pattern defects specifically along the A/P wing axis. The results show that the size of the Dpp expression domain is expanded in endocytosis-mutant wing discs. However, this expansion did not result in a concomitant expansion of the functional range of Dpp activity but rather its reduction as indicated by the reduced expression domain of the Dpp target gene spalt. The data suggest that clathrin-mediated endocytosis, a cellular process necessary for membrane recycling and vesicular trafficking, participates in Dpp action during wing development. Genetic interaction studies suggest a link between the Dpp receptors and clathrin. Impaired endocytosis does not interfere with the reception of the Dpp signal or the intracellular processing of the mediation of the signal in the responder cells, but rather affects the secretion and/or the distribution of Dpp in the developing wing cells. (+info)
Drosophila S6 kinase: a regulator of cell size.
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Cell proliferation requires cell growth; that is, cells only divide after they reach a critical size. However, the mechanisms by which cells grow and maintain their appropriate size have remained elusive. Drosophila deficient in the S6 kinase gene (dS6K) exhibited an extreme delay in development and a severe reduction in body size. These flies had smaller cells rather than fewer cells. The effect was cell-autonomous, displayed throughout larval development, and distinct from that of ribosomal protein mutants (Minutes). Thus, the dS6K gene product regulates cell size in a cell-autonomous manner without impinging on cell number. (+info)
Dfrizzled-3, a new Drosophila Wnt receptor, acting as an attenuator of Wingless signaling in wingless hypomorphic mutants.
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In Drosophila, two Frizzled proteins, Frizzled and Dfrizzled-2, have been reported to serve as receptors of Wingless. Here, we identified the third member of the Drosophila Frizzled family (Dfrizzled-3). In contrast to Dfrizzled-2, Dfrizzled-3 was transcriptionally upregulated by Wingless signaling. Although Dfrizzled-3 was capable of binding to Wingless in vitro, Wingless-dependent Armadillo/beta -catenin stabilization occurred much less effectively in Drosophila cells transfected with Dfrizzled-3 than in those with Dfrizzled-2. Flies lacking Dfrizzled-3 activity were viable and fertile, with few morphological defects. Genetic and immunochemical analysis indicated that the absence of Dfrizzled-3 activity suppresses the effects of hypomorphic wingless mutations such as failure of wing and antenna formation and restores target gene expression to the normal levels without change in wingless expression. Wingless signaling may thus be attenuated by Dfrizzled-3 at least in wingless hypomorphic mutants. (+info)
Drosophila myc regulates cellular growth during development.
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Transcription factors of the Myc proto-oncogene family promote cell division, but how they do this is poorly understood. Here we address the functions of Drosophila Myc (dMyc) during development. Using mosaic analysis in the fly wing, we show that loss of dMyc retards cellular growth (accumulation of cell mass) and reduces cell size, whereas dMyc overproduction increases growth rates and cell size. dMyc-induced growth promotes G1/S progression but fails to accelerate cell division because G2/M progression is independently controlled by Cdc25/String. We also show that the secreted signal Wingless patterns growth in the wing primordium by modulating dMyc expression. Our results indicate that dMyc links patterning signals to cell division by regulating primary targets involved in cellular growth and metabolism. (+info)
Mosquito hearing: sound-induced antennal vibrations in male and female Aedes aegypti.
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Male mosquitoes are attracted by the flight sounds of conspecific females. In males only, the antennal flagellum bears a large number of long hairs and is therefore said to be plumose. As early as 1855, it was proposed that this remarkable antennal anatomy served as a sound-receiving structure. In the present study, the sound-induced vibrations of the antennal flagellum in male and female Aedes aegypti were compared, and the functional significance of the flagellar hairs for audition was examined. In both males and females, the antennae are resonantly tuned mechanical systems that move as simple forced damped harmonic oscillators when acoustically stimulated. The best frequency of the female antenna is around 230 Hz; that of the male is around 380 Hz, which corresponds approximately to the fundamental frequency of female flight sounds. The antennal hairs of males are resonantly tuned to frequencies between approximately 2600 and 3100 Hz and are therefore stiffly coupled to, and move together with, the flagellar shaft when stimulated at biologically relevant frequencies around 380 Hz. Because of this stiff coupling, forces acting on the hairs can be transmitted to the shaft and thus to the auditory sensory organ at the base of the flagellum, a process that is proposed to improve acoustic sensitivity. Indeed, the mechanical sensitivity of the male antenna not only exceeds the sensitivity of the female antenna but also those of all other arthropod movement receivers studied so far. (+info)
Regulation of imaginal disc cell size, cell number and organ size by Drosophila class I(A) phosphoinositide 3-kinase and its adaptor.
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BACKGROUND: Class I(A) phosphoinositide 3-kinases (PI 3-kinases) have been implicated in the regulation of several cellular processes including cell division, cell survival and protein synthesis. The size of Drosophila imaginal discs (epithelial structures that give rise to adult organs) is maintained by factors that can compensate for experimentally induced changes in these PI 3-kinase-regulated processes. Overexpression of the gene encoding the Drosophila class I(A) PI 3-kinase, Dp110, in imaginal discs, however, results in enlarged adult organs. These observations have led us to investigate the role of Dp100 and its adaptor, p60, in the control of imaginal disc cell size, cell number and organ size. RESULTS: Null mutations in Dp110 and p60 were generated and used to demonstrate that they are essential genes that are autonomously required for imaginal disc cells to achieve their normal adult size. In addition, modulating Dp110 activity increases or reduces cell size in the developing imaginal disc, and does so throughout the cell cycle. The inhibition of Dp110 activity reduces the rate of increase in cell number in the imaginal discs, suggesting that Dp110 normally promotes cell division and/or cell survival. Unlike direct manipulation of cell-cycle progression, manipulation of Dp110 activity in one compartment of the disc influences the size of that compartment and the size of the disc as a whole. CONCLUSIONS: We conclude that during imaginal disc development, Dp110 and p60 regulate cell size, cell number and organ size. Our results indicate that Dp110 and p60 signalling can affect growth in multiple ways, which has important implications for the function of signalling through class I(A) PI 3-kinases. (+info)
An analysis of polygenes affecting wing shape on chromosome 3 in Drosophila melanogaster.
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Loci on the third chromosome of Drosophila melanogaster that affect an index of wing shape were mapped, using recombinant isogenic lines, with transposable elements as markers. Many genes with small subequal effects are dispersed along the whole chromosome. Their alleles act nearly additively in heterozygotes. They have small correlated effects on leg shape, but no detectable effects on halteres. Small negative net interactions occur over most of the chromosome. The data set of 519 recombinant isogenic lines can be explained reasonably well by two models. One model posits an indefinitely large number of loci with no interactions. The other model posits 11 loci with additive effects whose sum equals the total phenotypic range and with large positive and negative interactions that nearly cancel each other. (+info)