The Drosophila kismet gene was identified in a screen for dominant suppressors of Polycomb, a repressor of homeotic genes. Here we show that kismet mutations suppress the Polycomb mutant phenotype by blocking the ectopic transcription of homeotic genes. Loss of zygotic kismet function causes homeotic transformations similar to those associated with loss-of-function mutations in the homeotic genes Sex combs reduced and Abdominal-B. kismet is also required for proper larval body segmentation. Loss of maternal kismet function causes segmentation defects similar to those caused by mutations in the pair-rule gene even-skipped. The kismet gene encodes several large nuclear proteins that are ubiquitously expressed along the anterior-posterior axis. The Kismet proteins contain a domain conserved in the trithorax group protein Brahma and related chromatin-remodeling factors, providing further evidence that alterations in chromatin structure are required to maintain the spatially restricted patterns of ...
Insulin/insulin-like growth factor (IGF) plays an important role as a systemic regulator of metabolism in multicellular organisms. Hyperinsulinemia, a high level of blood insulin, is often associated with impaired physiological conditions such as hypoglycemia, insulin resistance, and diabetes. However, due to the complex pathophysiology of hyperinsulinemia, the causative role of excess insulin/IGF signaling has remained elusive. To investigate the biological effects of a high level of insulin in metabolic homeostasis and physiology, we generated flies overexpressing Drosophila insulin-like peptide 2 (Dilp2), which has the highest potential of promoting tissue growth among the Ilp genes in Drosophila. In this model, a UAS-Dilp2 transgene was overexpressed under control of sd-Gal4 that drives expression predominantly in developing imaginal wing discs. Overexpression of Dilp2 caused semi-lethality, which was partially suppressed by mutations in the insulin receptor (InR) or Akt1, suggesting that dilp2
Recommended Readings:. Chekulaeva, M. and A. Ephrussi. 2004. Drosophila Development: RNA Interference Ab Ovo. Current Biology 14 (11): R428-R430. Hachet, O. and A. Ephrussi. 2001. Drosophila Y14 Shuttles to the Posterior of the Oocyte and is Required for Oskar mRNA Transport. Current Biology 11 (21): 1666-1674. Jambor, H., C. Brunel, and A. Ephrussi. 2011. Dimerization of Oskar 3′ UTRs Promotes Hitchhiking for RNA Localization in the Drosophila Oocyte. RNA 17 (12): 2049-2057. Krauss, J., S. López de Quinto, C. Nüsslein-Volhard, and A. Ephrussi. 2009. Myosin-V Regulates Oskar mRNA Localization in the Drosophila Oocyte. Current Biology 19 (12): 1058-1063. Vanzo, N., A. Oprins, D. Xanthakis, A. Ephrussi, and C. Rabouille. 2007. Stimulation of Endocytosis and Actin Dynamics by Oskar Polarizes the Drosophila Oocyte. Developmental Cell 12 (4): 543-555. Vanzo, N. F. and A. Ephrussi. 2002. Oskar Anchoring Restricts Pole Plasm Formation to the Posterior of the Drosophila Oocyte. ...
THE imaginal discs of the Drosophila larva have long served as a model system in which to understand the control of organ size. Imaginal discs are epithelial sacs that, following metamorphosis, will form much of the adult tissue. The primordia of these discs are set aside in the embryo as small groups of 20-50 cells that remain diploid while much of the rest of the animal becomes polyploid. Over the 4 days that span the three larval instars, these primordia proliferate by ∼1000-fold to approach their final size. The size of the imaginal disc at the initiation of pupation is a major determinant of the size of the adult organ following metamorphosis. This size is highly regular, reflecting the importance for appropriate physiology and functioning of, for example, the complex optics of the compound eye or the aerodynamics of the wing and haltere flight organs. Thus, tight developmental controls must exist to permit sufficient but not excessive growth of the imaginal discs.. Classic and ...
Background: The modulation of mRNA levels across tissues and time is key for the establishment and operation of the developmental programs that transform the fertilized egg into a fully formed embryo. Although the developmental mechanisms leading to differential mRNA synthesis are heavily investigated, comparatively little attention is given to the processes of mRNA degradation and how these relate to the molecular programs controlling development. Results: Here we combine timed collection of Drosophila embryos and unfertilized eggs with genome-wide microarray technology to determine the degradation patterns of all mRNAs present during early fruit fly development. Our work studies the kinetics of mRNA decay, the contributions of maternally and zygotically encoded factors to mRNA degradation, and the ways in which mRNA decay profiles relate to gene function, mRNA localization patterns, translation rates and protein turnover. We also detect cis-regulatory sequences enriched in transcripts with ...
The microtubule (MT) cytoskeleton is reorganized during myogenesis as individual myoblasts fuse into multinucleated myotubes. Although this reorganization has long been observed in cell culture, these findings have not been validated during development, and proteins that regulate this process are largely unknown. A novel postmitotic function has been identified for the cytokinesis proteins RacGAP50C (Tumbleweed) and Pavarotti as essential regulators of MT organization during Drosophila myogenesis. The localization of the MT nucleator gamma-tubulin changes from diffuse cytoplasmic staining in mononucleated myoblasts to discrete cytoplasmic puncta at the nuclear periphery in multinucleated myoblasts, and this change in localization depends on RacGAP50C. RacGAP50C and gamma-tubulin colocalize at perinuclear sites in myotubes, and in RacGAP50C mutants gamma-tubulin remains dispersed throughout the cytoplasm. Furthermore, the mislocalization of RacGAP50C in pavarotti mutants is sufficient to ...
We show that generation of holes in the Drosophila embryo can substitute for the Tsl protein in the activation of the Torso Receptor Tyrosine Kinase (RTK) and t
We studied transcription during the first 14 mitotic cycles of Drosophila development, by gel electrophoresis of RNA pulse-labeled in vivo. Synthesis of rRNA, tRNAs, 5S RNAs, snRNAs, poly(A)+ RNAs, and histone mRNAs is first detectable during cycle 11 or 12. Histone genes are transcribed during S ph …
In this study, we demonstrate that Dscam endodomain variants are dynamically and differentially expressed in the developing Drosophila CNS. This conclusion derives from: (1) the analysis of Dscam transcript compositions by RT-PCR, (2) the localization of specific Dscam endodomains by depleting the alternatives via RNAi against exon 19, exon 23, or the unique exon-exon junctions derived from skipping of exon 19 or exon 23 (Fig. 2), and (3) the direct visualization of Dscam+19 using Ab19 as opposed to labeling all the Dscam isoforms with Ab18 (Fig. 3). Postembryonic neuronal morphogenesis uses Dscam variants lacking exons 19 and 23 (Fig. 4C), while Dscam+19 plays a more important role in the wiring of embryonic neural tracts (Fig. 4F). Skipping exon 19 prevents accumulation of Dscams in neuronal cell bodies, implicating a mechanism for regulating Dscam protein targeting by the alternative splicing of exon 19 (Figs. 6, 7). In addition, exon 23 is dispensable for most Dscam-dependent neuronal ...
Compartments are units of cell lineage that subdivide territories with different developmental potential. In Drosophila, the wing and haltere discs are subdivided into anterior and posterior (A/P) compartments, which require the activity of Hedgehog, and into dorsal and ventral (D/V) compartments, n …
The tubular epithelium of the Drosophila tracheal system forms a network with a stereotyped pattern consisting of cells and branches with distinct identity. The tracheal primordium undergoes primary branching induced by the FGF homolog Branchless, differentiates cells with specialized functions such as fusion cells, which perform target recognition and adhesion during branch fusion, and extends branches toward specific targets. Specification of a unique identity for each primary branch is essential for directed migration, as a defect in either the EGFR or the Dpp pathway leads to a loss of branch identity and the misguidance of tracheal cell migration. Here, we investigate the role of Wingless signaling in the specification of cell and branch identity in the tracheal system. Wingless and its intracellular signal transducer, Armadillo, have multiple functions, including specifying the dorsal trunk through activation of Spalt expression and inducing differentiation of fusion cells in all fusion ...
Signaling through the Hippo-Salvador-Warts (Wts) kinase cascade inhibits cell proliferation and promotes apoptosis by preventing nuclear accumulation of the transcriptional coactivator Yorkie (Yki in the fruit fly) or Yap (in vertebrates). Hippo-dependent phosphorylation of Yki by Wts prevents nuclear accumulation of Yki. In the nucleus, Yki cooperates with its partner Scalloped to promote expression of several target genes that inhibit apoptosis and promote mitosis. Two studies report that the serine-threonine kinase homeodomain-interacting protein kinase (Hipk) promotes Yki activity. Studies by Chen and Verheyen and by Poon et al. both demonstrate that, like overexpresison of yki or knockdown of wts, overexpresison of hipk in fly imaginal discs caused excessive cell proliferation, leading to tissue overgrowth, and stimulation of endogenous Yki transcriptional targets and reporter constructs. Reducing Hipk activity by mutation or RNA interference (RNAi) reduced both tissue size and expression ...
The Hippo pathway controls metazoan organ growth by regulating cell proliferation and apoptosis. Many components have been identified, but our knowledge of the composition and structure of this pathway is still incomplete. Using existing pathway components as baits, we generated by mass spectrometry a high-confidence Drosophila Hippo protein-protein interaction network (Hippo-PPIN) consisting of 153 proteins and 204 interactions. Depletion of 67% of the proteins by RNAi regulated the transcriptional coactivator Yorkie (Yki) either positively or negatively. We selected for further characterization a new member of the alpha-arrestin family, Leash, and show that it promotes degradation of Yki through the lysosomal pathway. Given the importance of the Hippo pathway in tumor development, the Hippo-PPIN will contribute to our understanding of this network in both normal growth and cancer.. ...
Wounding, apoptosis, or infection can trigger a proliferative response in neighboring cells to replace damaged tissue. Studies in Drosophila have implicated c-Jun amino-terminal kinase (JNK)-dependent activation of Yorkie (Yki) as essential to regeneration-associated growth, as well as growth associated with neoplastic tumors. Yki is a transcriptional coactivator that is inhibited by Hippo signaling, a conserved pathway that regulates growth. We identified a conserved mechanism by which JNK regulated Hippo signaling. Genetic studies in Drosophila identified Jub (also known as Ajuba LIM protein) as required for JNK-mediated activation of Yki and showed that Jub contributed to wing regeneration after wounding and to tumor growth. Biochemical studies revealed that JNK promoted the phosphorylation of Ajuba family proteins in both Drosophila and mammalian cells. Binding studies in mammalian cells indicated that JNK increased binding between the Ajuba family proteins LIMD1 or WTIP and LATS1, a kinase ...
Benign tumors accumulate mutations that enable them to progress to malignancy and metastasis. Although Yki overexpression promotes cell proliferation and inhibits apoptosis, Yki expression does not normally lead to the formation of malignant tumors in the Drosophila wing epithelia. Our findings show that inactivation of the BAP complex in discs expressing Yki results in the formation of giant larvae, a phenomenon characteristic of larvae with neoplastic tumors. The overgrown imaginal discs in these animals exhibit features of malignant transformation, including loss of epithelial polarity and expression of the proinvasive marker Mmp1. Moreover, when transplanted to a normal host, fragments of these discs produced tumors that grew and spread to kill the host.. The tumor suppressive role of the BAP complex appears to be context dependent. Overexpression of EGFR and Yki each results in tissue hyperplasia. Yki regulates cell proliferation and represses apoptosis by regulating target genes, including ...
The dorsoventral pattern of the Drosophila embryo is mediated by a gradient of nuclear localization of the dorsal protein which acts as amorphogen. Establishment of the nuclear concentration gradient of dorsal protein requires the activities of the 10 maternal dorsal group genes whose function results in the positive regulation of the nuclear uptake of the dorsal protein. Here we show that in contrast to the dorsal group genes, the maternal gene cactus acts as a negative regulator of the nuclear localization of the dorsal protein. While loss of function mutations of any of the dorsal group genes lead to dorsalized embryos, loss of cactusfunction results in a ventralization of the body pattern. Progressive loss of maternal cactus activity causes progressive loss of dorsal pattern elements accompanied by the expansion of ventrolateral and ventral anlagen. However, embryos still retain dorsoventral polarity, even if derived from germline clones using the strongest available, zygotic lethal cactus ...
Increasing evidence implicates the Hippo signalling pathway as a major mediator of contact inhibition of growth. In agreement with this model, genetic analysis in Drosophila and mice showed that this pathway restrains cell proliferation and promotes apoptosis to limit organ size and suppress tumorigenesis [[83],[84],[85]]. The core kinase cascade of this pathway-Hippo (MST1/2)-Salvador (WW45)-Warts (Lats1/2)-has been well characterized in Drosophila and is conserved in mammals, whereas its upstream regulation, which is rather complex, seems to have diverged after the separation of arthropods and chordates. In Drosophila, the atypical cadherin Fat and the apical polarity protein Crumbs activate the core kinase cascade through the FERM domain protein Expanded [[84],[86]]. Interestingly, genetic epistasis experiments showed that Merlin cooperates with Expanded to activate the Hippo pathway in the fly [[32]]. Mammalian cells lack a clear functional homologue of Fat [[87],[88]]. A recent study ...
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The Hippo pathway inactivates genes involved in organ size and when aberrant, can lead to cancer. To control organ size, the Hippo pathway inhibits Yorkie (Yki), a transcriptional coactivator that works with Scalloped (Sd), a DNA binding protein. When active, Yki translocates into the nucleus and initiates transcription. Conversely, when inactive, Yki remains in the cytoplasm. However, my work shows that cytoplasmic, inactive Yki interacts with other proteins in the Hippo pathway by recruiting them to the plasma membrane. Accordingly, this study challenges the notion that cytoplasmic Yki is inactive and instead, may play a dual role in the Hippo pathway.
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An exceptionally soft and smooth but also robust lightweight tartan - in our view the worlds finest. It will be woven to order for you, using traditional methods, by the worlds last artisan tartan weaving mill, deep in the Scottish Borders. Its an
Once upon a time, there was an excellent Italian tenor named Luciano Pavarotti.He didnt have the biggest voice in the world, or the sweetest. He didnt make the most dramatic of sounds, or the most
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Hi, I have a 7 yr old yorkie who I am concerned about but Im not sure if I have just been googling too much :) She currently weighs 8.5 down from 9.5 recently and 10 overall. We have been adamen...
TY - JOUR. T1 - Transcription control of a gene for Drosophila transcription factor, DREF by DRE and cis-elements conserved between Drosophila melanogaster and virilis. AU - Kwon, Eunjeong. AU - Seto, Hirokazu. AU - Hirose, Fumiko. AU - Ohshima, Nobuko. AU - Takahashi, Yasuhiko. AU - Nishida, Yasuyoshi. AU - Yamaguchi, Masamitsu. PY - 2003/5/8. Y1 - 2003/5/8. N2 - A DNA replication-related element (DRE)-binding factor (DREF) has been revealed to be an important transcription factor for activating promoters of cell proliferation and differentiation related genes. The amino acid sequences of DREF are conserved in evolutionary separate Drosophila species, Drosophila melanogaster (Dm) and Drosophila virilis (Dv) in three regions. In the present study, evidence was obtained that there are several highly conserved regions in the 5′ flanking region between the DmDREF and DvDREF genes. Band mobility shift assays using oligonucleotides corresponding to these conserved regions revealed that specific ...
We propose that the six genes previously classified as Polycomb group genes in which loss-of-function or antimorphic mutations show intergenic noncomplementation with mutations in trithorax group genes and increase the penetrance caused by double heterozygosis of mutations in trithorax group genes belong in a distinct group (Table 6). We propose that this group be called the ETP (Enhancers of trithorax and Polycomb mutations) group. Loss-of-function mutations in this group of genes enhance the dominant phenotype caused by Polycomb mutations like mutations in Polycomb group genes but also enhance the phenotype caused by heterozygosity for double mutations in trithorax group genes such as ash1VF101 trxb11 and brm2 trxe2 like mutations in trithorax group genes. Jürgens (1985) estimated that there were ∼40 genes in the Polycomb group based on the enhancement of the Polycomb mutant phenotype by a sample of deficiencies. We suggest that this number may be an overestimate. Many of the genes in which ...
Previous experiments have shown two germline stem cell genes, bam and bgcn, to be under strong positive selection in Drosophila melanogaster and Drosophila simulans (Bauer DuMont et al. 2007). This prompted the question of whether the same pattern of selection observed in these two species was present in the germline stem cell genes of other Drosophila lineages? The Aquadro Lab has been sequencing many germline stem cell genes in Drosophila species, and the answer to this question so far has been that some lineages show strong positive selection and some do not. This observation led the Aquadro Lab to begin to test hypotheses about the driver - or drivers - of the positive selection in the germline stem cell genes across some Drosophila lineages. One hypothesis proposed by Bauer DuMont et al. (2007) is that coevolution with pathogens such as the reproductive parasite, Wolbachia pipientis, infecting the germline could be driving this observed selection. This project looked for signs of selection ...
Cell adhesion molecule that plays a role in neuronal self-avoidance. Promotes repulsion between specific neuronal processes of either the same cell or the same subtype of cells. Mediates within retinal amacrine and ganglion cell subtypes both isoneuronal self-avoidance for creating an orderly dendritic arborization and heteroneuronal self-avoidance to maintain the mosaic spacing between amacrine and ganglion cell bodies (PubMed:10925149). Receptor for netrin required for axon guidance independently of and in collaboration with the receptor DCC. In spinal chord development plays a role in guiding commissural axons projection and pathfinding across the ventral midline to reach the floor plate upon ligand binding (PubMed:18585357, PubMed:19196994). Enhances netrin-induced phosphorylation of PAK1 and FYN (PubMed:15169762). Mediates intracellular signaling by stimulating the activation of MAPK8 and MAP kinase p38 (PubMed:18585357, PubMed:19196994). Adhesion molecule that promotes lamina-specific ...
Decapentaplegic (Dpp) is one of the best characterized morphogens, required for dorso-ventral patterning of the Drosophila embryo and for anterior-posterior (A/P) patterning of the wing imaginal disc. In the larval wing pouch, the Dpp target gene optomotor-blind (omb) is generally assumed to be expressed in a step function above a certain threshold of Dpp signaling activity. We show that the transcription factor Omb forms, in fact, a symmetrical gradient on both sides of the A/P compartment boundary. Disruptions of the Omb gradient lead to a re-organization of the epithelial cytoskeleton and to a retraction of cells toward the basal membrane suggesting that the Omb gradient is required for correct epithelial morphology. Moreover, by analysing the shape of omb gain- and loss-of-function clones, we find that Omb promotes cell sorting along the A/P axis in a concentration-dependent manner. Our findings show that Omb distribution in the wing imaginal disc is described by a gradient rather than a step
A protein encoded by a gene in band 22 of the long arm of human chromosome 21. The gene contains multiple exons which allow multiple mRNAs to be transcribed by alternative splicing (q.v.). The transcripts are differentially expressed in different substructures of the adult brain. The DSCAM is a member of the immunoglobulin domain superfamily (q.v.). These isoforms may be involved in the patterning of neural networks by selective adhesions between axons. See innate immunity. ...
Kitagawa M., Oyama T., Kawashima T., Yedvobnick B., Kumar A., Matsuno K., Harigaya K.. Mastermind (Mam) has been implicated as an important positive regulator of the Notch signaling pathway by genetic studies using Drosophila melanogaster. Here we describe a biochemical mechanism of action of Mam within the Notch signaling pathway. Expression of a human sequence related to Drosophila Mam (hMam-1) in mammalian cells augments induction of Hairy Enhancer of split (HES) promoters by Notch signaling. hMam-1 stabilizes and participates in the DNA binding complex of the intracellular domain of human Notch1 and a CSL protein. Truncated versions of hMam-1 that can maintain an association with the complex behave in a dominant negative fashion and depress transactivation. Furthermore, Drosophila Mam forms a similar complex with the intracellular domain of Drosophila Notch and Drosophila CSL protein during activation of Enhancer of split, the Drosophila counterpart of HES. These results indicate that Mam is ...
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TY - JOUR. T1 - Mutations that alter the timing and pattern of cubitus interruptus gene expression in Drosophila melanogaster. AU - Slusarski, D. C.. AU - Motzny, C. K.. AU - Holmgren, R.. PY - 1995/1/1. Y1 - 1995/1/1. N2 - The cubitus interruptus (ci) gene is a member of the Drosophila segment polarity gene family and encodes a protein with a zinc finger domain homologous to the vertebrate Gli genes and the nematode tra-1 gene. Three classes of existing mutations in the ci locus alter the regulation of ci expression and can be used to examine ci function during development. The first class of ci mutations causes interruptions in wing veins four and five due to inappropriate expression of the ci product in the posterior compartment of imaginal discs. The second class of mutations eliminates ci protein early in embryogenesis and causes the deletion of structures that are derived from the region including and adjacent to the engrailed expressing cells. The third class of mutations eliminates ci ...
TY - JOUR. T1 - The actin-binding protein Lasp promotes Oskar accumulation at the posterior pole of the Drosophila embryo. AU - Suyama, Ritsuko. AU - Jenny, Andreas. AU - Curado, Silvia. AU - Pellis-van Berkel, Wendy. AU - Ephrussi, Anne. PY - 2009/4/14. Y1 - 2009/4/14. N2 - During Drosophila oogenesis, oskar mRNA is transported to the posterior pole of the oocyte, where it is locally translated and induces germ-plasm assembly. Oskar protein recruits all of the components necessary for the establishment of posterior embryonic structures and of the germline. Tight localization of Oskar is essential, as its ectopic expression causes severe patterning defects. Here, we show that the Drosophila homolog of mammalian Lasp1 protein, an actin-binding protein previously implicated in cell migration in vertebrate cell culture, contributes to the accumulation of Oskar protein at the posterior pole of the embryo. The reduced number of primordial germ cells in embryos derived from lasp mutant females can be ...
In all Metazoa, transcription is inactive during the first mitotic cycles after fertilisation. In Drosophila melanogaster, Zygotic Genome Activation (ZGA) occurs in two waves, starting respectively at mitotic cycles 8 (approximately 60 genes) and 14 (over a thousand genes). The regulatory mechanisms underlying these drastic transcriptional changes remain largely unknown. We developed an original gene clustering method based on discretized transition profiles, and applied it to datasets from three landmark early embryonic transcriptome studies. We identified 417 genes significantly up-regulated during ZGA. De novo motif discovery returned nine motifs over-represented in their non-coding sequences (upstream, introns, UTR), three of which correspond to previously known transcription factors: Zelda, Tramtrack and Trithorax-like (Trl). The nine discovered motifs were combined to scan ZGA-associated regions and predict about 1300 putative cis-regulatory modules. The fact that Trl is known to act as chromatin
Author Summary Morphogens are signaling molecules that trigger specific responses in cells in a concentration-dependent manner. The formation of morphogen gradients is essential for the patterning of tissues and organs. Decapentaplegic (Dpp) is the Drosophila homolog of the bone morphogenic proteins in vertebrates and forms a morphogen gradient along the anterior-posterior axis of the Drosophila wing imaginal disc, a single-cell layered epithelium. Dpp determines the growth and final size of the wing disc and serves as an ideal model system to study gradient formation. Despite extensive studies the mechanism by which morphogen gradients are established remains controversial. In the case of Dpp two mechanisms have been postulated, namely extracellular diffusion and receptor-mediated transcytosis. In the first model Dpp is suggested to move by diffusion through the extracellular matrix of a tissue, whereas in the latter model Dpp is transported through the cells by receptor-mediated uptake and re
TY - JOUR. T1 - JAK/STAT and the GATA factor Pannier control hemocyte maturation and differentiation in Drosophila. AU - Minakhina, Svetlana. AU - Tan, William. AU - Steward, Ruth. PY - 2011/1/1. Y1 - 2011/1/1. N2 - The lymph gland is the major site of hematopoiesis in Drosophila. During late larval stages three types of hemocytes are produced, plasmatocytes, crystal cells, and lamellocytes, and their differentiation is tightly controlled by conserved factors and signaling pathways. JAK/STAT is one of these pathways which have essential roles in vertebrate and fly hematopoiesis. We show that Stat has opposing cell-autonomous and non-autonomous functions in hemocyte differentiation. Using a clonal approach we established that loss of Stat in a set of prohemocytes in the cortical zone induces plasmatocyte maturation in adjacent hemocytes. Hemocytes lacking Stat fail to differentiate into plasmatocytes, indicating that Stat positively and cell-autonomously controls plasmatocyte differentiation. We ...
In Drosophila embryos, checkpoints maintain genome stability by delaying cell cycle progression that allows time for damage repair or to complete DNA synthesis. Drosophila MOF, a member of MYST histone acetyl transferase is an essential component of male X hyperactivation process. Until recently its involvement in G2/M cell cycle arrest and defects in ionizing radiation induced DNA damage pathways was not well established. Drosophila MOF is highly expressed during early embryogenesis. In the present study we show that haplo-insufficiency of maternal MOF leads to spontaneous mitotic defects like mitotic asynchrony, mitotic catastrophe and chromatid bridges in the syncytial embryos. Such abnormal nuclei are eliminated and digested in the yolk tissues by nuclear fall out mechanism. MOF negatively regulates Drosophila checkpoint kinase 2 tumor suppressor homologue. In response to DNA damage the checkpoint gene Chk2 (Drosophila mnk) is activated in the mof mutants, there by causing centrosomal inactivation
Monoclonal antibodies were prepared against a 46,000 mol wt major cytoplasmic protein from Drosophila melanogaster Kc cells. These antibodies reacted with the 46,000 and a 40,000 mol wt protein from Kc cells. Some antibodies showed cross-reaction with 55,000 (vimentin) and 52,000 mol wt (desmin) proteins from baby hamster kidney (BHK) cells that form intermediate sized filaments in vertebrate cells. In indirect immunofluorescence, the group of cross reacting antibodies stained a filamentous meshwork in the cytoplasm of vertebrate cells. In Kc cells the fluorescence seemed to be localized in a filamentous meshwork that became more obvious after the cells had flattened out on a surface. These cytoskeletal structures are heat-labile; the proteins in Kc or BHK cells rearrange after a brief heat shock, forming juxtanuclear cap structures.
Smaug is an RNA-binding protein that induces the degradation and represses the translation of mRNAs in the early Drosophila embryo. Smaug has two identified direct target mRNAs that it differentially regulates: nanos and Hsp83. Smaug represses the translation of nanos mRNA but has only a modest effect on its stability, whereas it destabilizes Hsp83 mRNA but has no detectable effect on Hsp83 translation. Smaug is required to destabilize more than one thousand mRNAs in the early embryo, but whether these transcripts represent direct targets of Smaug is unclear and the extent of Smaug-mediated translational repression is unknown. To gain a panoramic view of Smaug function in the early embryo, we identified mRNAs that are bound to Smaug using RNA co-immunoprecipitation followed by hybridization to DNA microarrays. We also identified mRNAs that are translationally repressed by Smaug using polysome gradients and microarrays. Comparison of the bound mRNAs to those that are translationally repressed by Smaug
Cyclin Y is a highly conserved member of the Cyclin superfamily of proteins. In Drosophila the Cyclin Y gene (CycY) is required for progression through several stages of development but the specific pathways that Cyclin Y belongs to and that account for its requirement are not known. Studies in human and Drosophila cell lines have shown that membrane-localized Cyclin Y is required for phosphorylation of the wingless/Wnt co-receptor, arrow/LRP6, and for full activation of the canonical wingless/Wnt pathway. CycY null Drosophila, however, do not phenocopy loss-of-function mutations in canonical wingless pathway genes, suggesting that Cyclin Y may have additional roles outside the wingless pathway in vivo. To identify roles for Cyclin Y in Drosophila I used RNAi to knock down CycY expression in 31 distinct tissue patterns. The screen revealed that expression of the CycY shRNA in specific tissue patterns causes larval lethality and other developmental defects. Knockdown of CycY but not arrow in imaginal
N6-methyladenosine (m6A) is the most common internal modification of eukaryotic messenger RNA (mRNA) and is decoded by YTH domain proteins1, 2, 3, 4, 5, 6, 7. The mammalian mRNA m6A methylosome is a complex of nuclear proteins that includes METTL3 (methyltransferase-like 3), METTL14, WTAP (Wilms tumour 1-associated protein) and KIAA1429. Drosophila has corresponding homologues named Ime4 and KAR4 (Inducer of meiosis 4 and Karyogamy protein 4), and Female-lethal (2)d (Fl(2)d) and Virilizer (Vir)8, 9, 10, 11, 12. In Drosophila, fl(2)d and vir are required for sex-dependent regulation of alternative splicing of the sex determination factor Sex lethal (Sxl)13. However, the functions of m6A in introns in the regulation of alternative splicing remain uncertain3. Here we show that m6A is absent in the mRNA of Drosophila lacking Ime4. In contrast to mouse and plant knockout models5, 7, 14, Drosophila Ime4-null mutants remain viable, though flightless, and show a sex bias towards maleness. This is ...
Binding of pumilio to maternal hunchback mRNA is required for posterior patterning in Drosophila embryos. Developmental regulation of vesicle transport in Drosophila embryos: forces and kinetics
The JAK/STAT pathway is an essential signalling cascade required for multiple processes during development and for adult homeostasis. A key question in understanding this pathway is how it is regulated in different cell contexts. Here we have examined how endocytic processing contributes to signalling by the single cytokine receptor, Domeless, in Drosophila melanogaster cells. We identify an evolutionarily conserved di-Leu motif that is required for Domeless internalisation and show that endocytosis is required for activation of a subset of Domeless targets. Our data indicate that endocytosis both qualitatively and quantitatively regulates Domeless signalling. STAT92E, the single STAT transcription factor in Drosophila, appears to be the target of endocytic regulation and our studies show that phosphorylation of STAT92E on Tyr704, while necessary, is not always sufficient for target transcription. Finally, we identify a conserved residue, Thr702, which is essential for Tyr704 phosphorylation. ...
Mating rate is a major determinant of female lifespan and fitness, and is predicted to optimize at an intermediate level, beyond which superfluous matings are costly. In female Drosophila melanogaster, nutrition is a key regulator of mating rate but the underlying mechanism is unknown. The evolutionarily conserved insulin/insulin-like growth factor-like signalling (IIS) pathway is responsive to nutrition, and regulates development, metabolism, stress resistance, fecundity and lifespan. Here we show that inhibition of IIS, by ablation of Drosophila insulin-like peptide (DILP)-producing median neurosecretory cells, knockout of dilp2, dilp3 or dilp5 genes, expression of a dominant-negative DILP-receptor (InR) transgene or knockout of Lnk, results in reduced female remating rates. IIS-mediated regulation of female remating can occur independent of virgin receptivity, developmental defects, reduced body size or fecundity, and the receipt of the female receptivity-inhibiting male sex peptide. Our ...
TY - JOUR. T1 - DCtBP mediates transcriptional repression by Knirps, Kruppel and Snail in the Drosophila embryo. AU - Nibu, Yutaka. AU - Zhang, Hailan. AU - Bajor, Ewa. AU - Barolo, Scott. AU - Small, Stephen. AU - Levine, Michael. PY - 1998/12/1. Y1 - 1998/12/1. N2 - The pre-cellular Drosophila embryo contains 10 well characterized sequence-specific transcriptional repressors, which represent a broad spectrum of DNA-binding proteins. Previous studies have shown that two of the repressors, Hairy and Dorsal, recruit a common co-repressor protein, Groucho. Here we present evidence that three different repressors, Knirps, Kruppel and Snail, recruit a different co-repressor, dCtBP. Mutant embryos containing diminished levels of maternal dCtBP products exhibit both segmentation and dorsoventral patterning defects, which can be attributed to loss of Kruppel, Knirps and Snail activity. In contrast, the Dorsal and Hairy repressors retain at least some activity in dCtBP mutant embryos, dCtBP interacts ...
In multicellular organisms all cells in one individual have an identical genotype, and yet their bodies consist of many and very different tissues and thus many different cell types. Somehow there must be a difference in how genes are interpreted. So, there must be signals that tell the genes when and where to be active and inactive, respectively. In some instances a specific an expression pattern (active or inactive) is epigenetic; it is established and maintained throughout multiple rounds of cell divisions. In the developing Drosophila embryo, the proper expression pattern of e.g. the homeotic genes Abd-B and Ubx is to be kept active in the posterior part and silenced in the anterior. Properly silenced homeotic genes are crucial for the correct segmentation pattern of the fly and the Polycomb group (Pc-G) proteins are vital for maintaining this type of stable repression.. As part of this thesis, Suppressor of zeste 12 (Su(z)12) is characterized as a Drosophila Pc-G gene. Mutations in the gene ...
Remarkably, a motif corresponding to the Tramtrack (TTK) binding motif was discovered with the de novo approach. TTK is a maternal repressor, which is progressively titrated as the NC ratio increases during early mitotic cycles, thereby releasing the expression of zygotic genes [5]. Surprisingly, the TTK binding motif is found over-represented in the sequences of pre-cellular activated blastoderm genes and of the genes with the discrete signature Lu u s D s s H , but not in the sequences of genes known to depend on the NC ratio, which might be explained by the intervention of some other factors in this mechanism [5].. The TTK protein has been reported to physically interact with TRL proteins and to repress TRL-mediated even-skipped activation [20]. TTK could act either directly by binding DNA and repressing the transcription of specific target genes, or indirectly by repressing an activator such as Trl. Interestingly, the TTK motif is significantly under-represented (sig = 5) in upstream ...
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Background: The family of c-Jun NH2-terminal kinases (JNK) plays important roles in embryonic development and in cellular responses to stress. Toxic metals and their compounds are potent activators of JNK in mammalian cells. The mechanism of mammalian JNK activation by cadmium and sodium arsenite involves toxicant-induced oxidative stress. The study of mammalian signaling pathways to JNK is complicated by the significant degree of redundancy among upstream JNK regulators, especially at the level of JNK kinase kinases (JNKKK). Results: Using Drosophila melanogaster S2 cells, we demonstrate here that cadmium and arsenite activate Drosophila JNK (D-JNK) via oxidative stress as well, thus providing a simpler model system to study JNK signaling. To elucidate the signaling pathways that lead to activation of D-JNK in response to cadmium or arsenite, we employed RNA interference (RNAi) to knock down thirteen upstream regulators of D-JNK, either singly or in combinations of up to seven at a time. Conclusion: D
Acar, M., et al. (2006). Senseless physically interacts with proneural proteins and functions as a transcriptional co-activator. Development 133: 1979-1989. PubMed ID: 16624856 Alifragis, P., et al. (1997). A network of interacting transcriptional regulators involved in Drosophila neural fate specification revealed by the yeast two-hybrid system. Proc. Natl. Acad. Sci. 94(24): 13099-13104. PubMed ID: 9371806 Bardin, A. J., et al. (2010). Transcriptional control of stem cell maintenance in the Drosophila intestine. Development 137(5): 705-14. PubMed ID: 20147375 Barndt, R. J., Dai, M. and Zhuang, Y. (2000). Functions of E2A-HEB heterodimers in T-cell development revealed by a dominant negative mutation of HEB. Mol. Cell Biol. 20: 6677-6685. PubMed ID: 10958665 Brown, N. L., et al. (1996). daughterless is required for Drosophila photoreceptor cell determination, eye morphogenesis, and cell cycle progression. Dev. Biol. 179: 65-78. PubMed ID: 8873754 Buszczak, M., Paterno, S. and Spradling, A. C. ...
TY - JOUR. T1 - Activation of a meiotic checkpoint regulates translation of Gurken during Drosophila oogenesis. AU - Ghabrial, Amin. AU - Schüpbach, Trudi. N1 - Funding Information: ACKNOWLEDGEMENTS We thank K. McKim, J. Sekelsky, S. Hawley, S. Wayson and R. Ray for mutant stocks and helpful discussions; C. VanBuskirk for sharing anti-Grk monoclonal antibodies; I. Clark for Vasa reagents and advice on Vasa westerns; G. Shanower, G. Deshpande and P. Schedl for their advice; and E. Wieschaus, L. Nilson, C. VanBuskirk and A. Norvell for comments on the manuscript. This work was supported by the US Public Health Service grant PO1 CA 41086 and the HHMI. Correspondence and requests for materials should be addressed to T.S.. PY - 1999/10. Y1 - 1999/10. N2 - The genes okra and spindle-B act during meiosis in Drosophila to repair double-stranded DNA breaks (DSBs) associated with meiotic recombination. Unexpectedly, mutations in these genes cause dorsoventral patterning defects during oogenesis. These ...
Polyamine transport is elevated in many tumor types, suggesting that toxic polyamine-drug conjugates could be targeted to cancer cells via the polyamine transporter (PAT). We have previously reported the use of Chinese hamster ovary (CHO) cells and its PAT-deficient mutant cell line, CHO-MG, to screen anthracene-polyamine conjugates for their PAT-selective targeting ability. We report here a novel Drosophila-based model for screening anthracene-polyamine conjugates in a developing and intact epithelium (Drosophila imaginal discs), wherein cell-cell adhesion properties are maintained. Data from the Drosophila assay are consistent with previous results in CHO cells, indicating that the Drosophila epithelium has a PAT with vertebrate-like characteristics. This assay will be of use to medicinal chemists interested in screening drugs that use PAT for cellular entry, and it offers the possibility of genetic dissection of the polyamine transport process, including identification of a Drosophila PAT.
TY - JOUR. T1 - Molecular cloning of the Drosophila melanogaster gene χ5 dm encoding a 20S proteasome χ-type subunit. AU - Zaiss, Dietmar. AU - Belote, John M.. N1 - Funding Information: We would like to thank Dr Russ Finley for the pJG4-5 cDNA library and Dr Kerrie-Ann Smyth for providing the salivary gland chromosome squashes for the in situ hybridization experiment, Evan Katz for carrying out the reduced stringency hybridization screen, and Xiaoqing Yuan for mapping Pros29 (a3_dm). We would also like to thank Jing Ma, Mary Miller and Kerrie-Ann Smyth for their helpful comments on the manuscript. This material is based upon work supported by the National Science Foundation under Grant No. MCB-9506885. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation.. PY - 1997/11/12. Y1 - 1997/11/12. N2 - Proteasomes are large, multisubunit particles that act as the ...
Zhu LJ, Christensen RG, Kazemian M, Hull CJ, Enuameh MS, Basciotta MD, Brasefield JA, Zhu C, Asriyan Y, Lapointe DS, Sinha S, Wolfe SA, Brodsky MH. FlyFactorSurvey: a database of Drosophila transcription factor binding specificities determined using the bacterial one-hybrid system. Nucleic Acids Res. 2011 Jan; 39(Database issue):D111-7 ...
The human c-myc proto-oncogene, implicated in the control of many cellular processes including cell growth and apoptosis, encodes three isoforms which differ in their N-terminal region. The functions of these isoforms have never been addressed in vivo. Here, we used Drosophila melanogaster to examine their functions in a fully integrated system. First, we established that the human c-Myc protein can rescue lethal mutations of the Drosophila myc ortholog, dmyc, demonstrating the biological relevance of this model. Then, we characterized a new lethal dmyc insertion allele, which permits expression of human c-Myc in place of dMyc and used it to compare physiological activities of these isoforms in whole-organism rescue, transcription, cell growth, and apoptosis. These isoforms differ both quantitatively and qualitatively. Most remarkably, while the small c-MycS form truncated for much of its N-terminal trans-activation domain efficiently rescued viability and cell growth, it did not induce ...
An in vivo screen of 86 RNAi lines, representing the majority of annotated Drosophila phosphatases/regulators, for altered activity rhythms was carried out. The screen identified a total of 19 candidate genes (Table 1) that altered clock function upon RNAi knockdown in Drosophila clock cells. Further genetic validation of one candidate showed that the RPTP Lar is required for the development of axonal projections from circadian pacemaker neurons that support rhythmic activity in constant darkness but not during light:dark cycles (Agrawal and Hardin 2016).. As expected, a majority of these candidates were not validated upon further analysis of independent genetic reagents (Table 2). However, these reagents consisted of additional P element inserts, where the P element insertion site may not interfere with gene function, or strains that could be used for overexpression, which also may not impact the function of a protein that is already at saturating levels. Therefore, a lack of validation with P ...
Receptors for Wingless and other signalling molecules of the Wnt gene family have yet to be identified. We show here that cultured Drosophila cells transfected with a novel member of the frizzled gene family in Drosophila, Dfz2, respond to added Wingless protein by elevating the level of the Armadillo protein. Moreover, Wingless binds to Drosophila or human cells expressing Dfz2. These data demonstrate that Dfz2 functions as a Wingless receptor, and they imply, in general, that Frizzled proteins are receptors for the Wnt signalling molecules ...
Applications are invited for a postdoc position and a full-time technician = position in Drosophila epigenetics research laboratory of Dr. Tulin at the = Fox Chase Cancer Center, Philadelphia, PA. Both positions planned for at = least three years, with possible renewal. The successful applicants will = use Drosophila model system to study epigenetics of development and = cancer. The primary research focus of Dr. Tulin=92s lab is on = fundamentals of chromatin reprogramming and RNA fate regulation during = normal development and carcinogenics, as well as on translating = fundamental research for clinical applications in oncology. Projects in = Dr. Tulin=92s lab cover the molecular mechanisms of the chromatin = remodeling and regulation of gene expression and employ Drosophila model = and in vitro assays as well as human cells, mouse models. Applicants for the postdoctoral position should have a Ph.D. in molecular = biology, molecular genetics, biochemistry, or a related field and 0-3 = years of ...
Circularization was recently recognized to broadly expand transcriptome complexity. Here, we exploit massive Drosophila total RNA-sequencing data, |5 billion paired-end reads from |100 libraries covering diverse developmental stages, tissues, and cultured cells, to rigorously annotate |2,500 fruit fly circular RNAs. These mostly derive from back-splicing of protein-coding genes and lack poly(A) tails, and the circularization of hundreds of genes is conserved across multiple Drosophila species. We elucidate structural and sequence properties of Drosophila circular RNAs, which exhibit commonalities and distinctions from mammalian circles. Notably, Drosophila circular RNAs harbor |1,000 well-conserved canonical miRNA seed matches, especially within coding regions, and coding conserved miRNA sites reside preferentially within circularized exons. Finally, we analyze the developmental and tissue specificity of circular RNAs and note their preferred derivation from neural genes and enhanced accumulation in