| 1. |
- Grönholm, Juha, et al.
(author)
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Not4 enhances JAK/STAT pathway-dependent gene expression in Drosophila and in human cells
- 2012
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In: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 26:3, s. 1239-1250
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Journal article (peer-reviewed)abstract
- The JAK/STAT pathway is essential for organogenesis, innate immunity, and stress responses in Drosophila melanogaster. The JAK/STAT pathway and its associated regulators have been highly conserved in evolution from flies to humans. We have used a genome-wide RNAi screen in Drosophila S2 cells to identify regulators of the JAK/STAT pathway, and here we report the characterization of Not4 as a positive regulator of the JAK/STAT pathway. Overexpression of Not4 enhanced Stat92E-mediated gene responses in vitro and in vivo in Drosophila. Specifically, Not4 increased Stat92E-mediated reporter gene activation in S2 cells; and in flies, Not4 overexpression resulted in an 8-fold increase in Turandot M (TotM) and in a 4-fold increase in Turandot A (TotA) stress gene activation when compared to wild-type flies. Drosophila Not4 is structurally related to human CNOT4, which was found to regulate interferon-gamma- and interleukin-4-induced STAT-mediated gene responses in human HeLa cells. Not4 was found to coimmunoprecipitate with Stat92E but not to affect tyrosine phosphorylation of Stat92E in Drosophila cells. However, Not4 is required for binding of Stat92E to its DNA recognition sequence in the TotM gene promoter. In summary, Not4/CNOT4 is a novel positive regulator of the JAK/STAT pathway in Drosophila and in humans.
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| 2. |
- Jacobsson, Linn, 1977-, et al.
(author)
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The Drosophila Pax6 paralogs have different functions in head development but can partially substitute for each other
- 2009
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In: Molecular Genetics and Genomics. - : Springer Science and Business Media LLC. - 1617-4615 .- 1617-4623. ; 282:3, s. 217-231
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Journal article (peer-reviewed)abstract
- There are two Pax6 genes in Drosophila melanogaster; eyeless (ey) and twin-of-eyeless (toy), due to a duplication, which most likely occurred in the insect lineage. They encode transcription factors important for head development. Misexpression of either toy or ey can induce formation of ectopic compound eyes. Toy regulates the ey gene by binding to an eye-specific enhancer in its second intron. However, Toy can induce ectopic eyes also in an ey( - ) background, which indicates a redundancy between the two Pax6 copies in eye formation. To elucidate to what extent these two genes are interchangeable, we first generated toy-Gal4 constructs capable of driving the Pax6 genes in a toy-specific manner. Genetic dissection of the promoter proximal region of toy identified a 1,300-bp region around the canonical transcription start that is sufficient to drive toy expression in embryonic brain and eye primorida and in larval eye-antennal discs. We find that exogenous expression of toy can partially rescue the lethality and eye phenotype caused by lethal mutations in ey and vice versa. We therefore conclude that Toy and Ey, to some extent, can substitute for each other. Nevertheless, the phenotypes of the rescued flies indicate that the two Pax6 genes are specialized to regulate defined structures of the fly head.
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| 3. |
- Kronhamn, Jesper, 1966-
(author)
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Genetic analysis of genes found on the 4th chromosome of Drosophila - emphasizing the developmental context of Pax6
- 2004
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Doctoral thesis (other academic/artistic)abstract
- The small size and the lack of recombination set the fourth chromosome of Drosophila melanogaster apart from the other chromosomes. I have shown that the Minute gene on chromosome 4, earlier named Minute-4, encodes the ribosomal protein RpS3A. Two Pax6 genes, eyeless (ey) and twin of eyeless (toy) are also located on chromosome 4.Pax6 genes are important in head and eye development in both mammals and Drosophila. I have focused much of the study on ey and toy. The first mutant of toy that was characterized showed a headless phenotype. This indicates that Toy is important for the development of both the eye and antennal discs. The phenotype of the null mutation in toy is temperature sensitive due to that transcription of ey is temperature dependent in the eye-antennal primordium in absence of Toy. This temperature dependence was used to find out that the phenocritical period for ey in the adult head development is during embryonic stage 12-16 when ey first is expressed in the eye-antennal primordium. I also conclude that ey is activated by Toy in the eye-antennal primordium.The strong eyD mutation was molecularly characterized and it was finally settled that it is an allele in the ey locus. I also show that eyD homozygotes have a headless phenotype, much stronger than the earlier ey mutations.
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| 4. |
- Kronhamn, Jesper, et al.
(author)
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Genetic organization of the ci-M-pan region on chromosome IV in Drosophila melanogaster.
- 1999
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In: Genome. - 0831-2796 .- 1480-3321. ; 42:6, s. 1144-1149
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Journal article (peer-reviewed)abstract
- The genes cubitus interruptus (ci), ribosomal protein S3A (RpS3A), and pangolin (pan) are localized within 73 kb in the cytological region 101F-102A on chromosome IV in Drosophila melanogaster. A region of 13 kb harbours the regulatory regions of both ci and pan, transcribed in opposite directions, and a 1.1-kb gene encoding RpS3A. This dense clustering gives rise to very complicated complementation patterns between different alleles in these loci. We investigated this region genetically and molecularly by use of an enhancer trap line (IA5), where the P-element was found to be inserted into the first intron of pan. Screens for imprecise excisions of the P-element were performed, and complementations between new and old established mutant lines were investigated. We found that when mutated or deleted the RpS3A gene gives rise to a Minute phenotype, and we conclude that M(4)101 encodes the ribosomal protein S3A.
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| 5. |
- Kronhamn, Jesper, et al.
(author)
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Headless flies produced by mutations in the paralogous Pax6 genes eyeless and twin of eyeless.
- 2002
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In: Development. - 0950-1991 .- 1477-9129. ; 129:4, s. 1015-1026
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Journal article (peer-reviewed)abstract
- The two Pax6 gene homologs eyeless and twin of eyeless play decisive early roles in Drosophila eye development. Strong mutants of twin of eyeless or of eyeless are headless, which suggests that they are required for the development of all structures derived from eye-antennal discs. The activity of these genes is crucial at the very beginning of eye-antennal development in the primordia of eye-antennal discs when eyeless is first activated by the twin of eyeless gene product. This activation does not strictly depend on the Twin of eyeless protein, but is temperature-dependent in its absence. Twin of eyeless acts also in parallel to the eyeless gene and exerts functions that are partially redundant with those of Eyeless, while Eyeless is mainly required to prevent early cell death and promote eye development in eye-antennal discs.
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| 6. |
- Márkus, Róbert, et al.
(author)
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Sessile hemocytes as a hematopoietic compartment in Drosophila melanogaster
- 2009
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 106:12, s. 4805-4809
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Journal article (peer-reviewed)abstract
- The blood cells, or hemocytes, in Drosophila participate in the immune response through the production of antimicrobial peptides, the phagocytosis of bacteria, and the encapsulation of larger foreign particles such as parasitic eggs; these immune reactions are mediated by phylogenetically conserved mechanisms. The encapsulation reaction is analogous to the formation of granuloma in vertebrates, and is mediated by large specialized cells, the lamellocytes. The origin of the lamellocytes has not been formally established, although it has been suggested that they are derived from the lymph gland, which is generally considered to be the main hematopoietic organ in the Drosophila larva. However, it was recently observed that a subepidermal population of sessile blood cells is released into the circulation in response to a parasitoid wasp infection. We set out to analyze this phenomenon systematically. As a result, we define the sessile hemocytes as a novel hematopoietic compartment, and the main source of lamellocytes.
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| 7. |
- Schmid, Martin R., et al.
(author)
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Genetic Screen in Drosophila Larvae Links ird1 Function to Toll Signaling in the Fat Body and Hemocyte Motility
- 2016
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Journal article (peer-reviewed)abstract
- To understand how Toll signaling controls the activation of a cellular immune response in Drosophila blood cells (hemocytes), we carried out a genetic modifier screen, looking for deletions that suppress or enhance the mobilization of sessile hemocytes by the gain-of-function mutation Toll(10b) (Tl-10b). Here we describe the results from chromosome arm 3R, where five regions strongly suppressed this phenotype. We identified the specific genes immune response deficient 1 (ird1), headcase (hdc) and possibly Rab23 as suppressors, and we studied the role of ird1 in more detail. An ird1 null mutant and a mutant that truncates the N-terminal kinase domain of the encoded Ird1 protein affected the Tl-10b phenotype, unlike mutations that affect the C-terminal part of the protein. The ird1 null mutant suppressed mobilization of sessile hemocytes, but enhanced other Tl-10b hemocyte phenotypes, like the formation of melanotic nodules and the increased number of circulating hemocytes. ird1 mutants also had blood cell phenotypes on their own. They lacked crystal cells and showed aberrant formation of lamellocytes. ird1 mutant plasmatocytes had a reduced ability to spread on an artificial substrate by forming protrusions, which may explain why they did not go into circulation in response to Toll signaling. The effect of the ird1 mutation depended mainly on ird1 expression in hemocytes, but ird1-dependent effects in other tissues may contribute. Specifically, the Toll receptor was translocated from the cell membrane to intracellular vesicles in the fat body of the ird1 mutant, and Toll signaling was activated in that tissue, partially explaining the Tl-10b-like phenotype. As ird1 is otherwise known to control vesicular transport, we conclude that the vesicular transport system may be of particular importance during an immune response.
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| 8. |
- Yang, Hairu, et al.
(author)
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JAK/STAT signaling in Drosophila muscles controls the cellular immune response against parasitoid infection
- 2015
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In: EMBO Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 16:12, s. 1664-1672
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Journal article (peer-reviewed)abstract
- The role of JAK/STAT signaling in the cellular immune response of Drosophila is not well understood. Here, we show that parasitoid wasp infection activates JAK/STAT signaling in somatic muscles of the Drosophila larva, triggered by secretion of the cytokines Upd2 and Upd3 from circulating hemocytes. Deletion of upd2 or upd3, but not the related os (upd1) gene, reduced the cellular immune response, and suppression of the JAK/STAT pathway in muscle cells reduced the encapsulation of wasp eggs and the number of circulating lamellocyte effector cells. These results suggest that JAK/STAT signaling in muscles participates in a systemic immune defense against wasp infection.
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