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1 Venture Laboratory, Kyoto Institute of Technology, Sakyo-ku, Kyoto, Japan;
2 Department of Applied Biology, Kyoto Institute of Technology, Sakyo-ku, Kyoto, Japan;
3 Division of Biochemistry, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya, Japan
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Abstract |
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Introduction |
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and proliferating-cell nuclear antigen (PCNA), dE2F, cyclin A, D-ras2 and D-raf, contain a common 8-bp palindromic sequence (5'-TATCGATA) named the DNA replication-related element (DRE) (Hirose et al. 1993), in addition to E2F-binding sites (Duronio et al. 1995; Yamaguchi et al. 1995a). The requirement of this DRE for promoter activity has been confirmed in both cultured cells and transgenic flies (Yamaguchi et al. 1995b, Hirose et al. 1996; Yamaguchi et al. 1996) and we have found a specific DRE-binding factor (DREF), an 80-kDa polypeptide homodimer, and molecular cloning of its cDNA has led to confirmation that DREF is a trans-activator for DRE-containing genes. By searching the Drosophila genome database, we found DRE-like sequences in the 5'-flanking regions of many genes other than those which are DNA replication- and proliferation-related (Matsukage et al. 1995). Very recently, it was reported that 277 genes contain DRE-like sequences within their promoter regions (Ohler et al. 2002) and immunostaining of polytene chromosomes of salivary glands with an anti-DREF monoclonal antibody revealed that DREF binds to hundreds of regions of polytene chromosomes (Hirose et al. 2002), suggesting that DREF might regulate the expression of many genes and play multiple roles in vivo. The most direct way of addressing the biological roles of DREF in living flies is to analyse phenotypes associated with mutations in the DREF gene. Although a fly line, DrefKG09294 , having a P-element insertion in the 5'-flanking region of the DREF gene is now available at Bloomington Stock Center, a homozygote of the fly line is viable and DREF mRNA is still detectable in the homozygote flies. We have tried to isolate the DREF mutant by imprecise excision of the DrefKG09294 element, but it is so far not successful. We have therefore established transgenic fly lines over-expressing DREF protein or inducing inverted repeat RNA of the DREF gene (dref-IR) in various tissues at various developmental stages by utilizing the GAL4-UAS targeted expression system (Brand & Perrimon 1993), which allows a rapid generation of individual strains in which ectopic expression or knocking down of target gene expression can be directed to different tissues or cell types. Recently, we reported that over-expression of DREF in the posterior compartment in the wing imaginal discs induces apoptosis and leads to a notched wing phenotype (Yoshida et al. 2001). Although another phenotype, featuring vein enlargement, was observed with over-expression of DREF, the precise role of DREF in wing development has yet to be clarified.
Vein tissue specification occurs during larval and pupal stages within the wing imaginal discs and involves a complex network of gene interactions. Central to this network is the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase (RTK) (Diaz-Benjumea & Hafen 1994), which, in Drosophila, functions in a wide spectrum of developmental processes such as oogenesis, patterning of embryonic structures such as the ventral epidermis and trachea, and specification of photoreceptor cells in the compound eye (Schweitzer & Shilo 1997). In the wing imaginal disc, activation of EGFR in rows of cells causes their determination as prospective wing veins. Consistent with this, loss-of-function mutations in components of the EGFR pathway cause loss of veins, whereas gain-of-function alleles and/or over-expression of those components result in ectopic vein development (Diaz-Benjumea & Hafen 1994).
The present study revealed that DREF activates the EGFR signalling pathway, at least in part, during wing vein development. Over-expression of DREF was thus found to induce ectopic activation of EGFR signalling and result in increased width of the L5 vein close to the wing margin. In addition, reduction of DREF by expression of dref-IR in the posterior compartment of wing discs resulted in loss of L5 veins around the wing blade. These data suggest that DREF is involved in the formation of L5 veins close to the wing mirgin.
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Results |
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In Drosophila, injected double-stranded RNA (dsRNA) acts as a potent and specific inhibitor of gene expression and this method of gene expression blockage are called RNA interference (RNAi) (Kennerdell & Carthew 1998; Misquitta & Paterson 1999). We established seven and 13 independent transgenic fly lines carrying UAS-dref-IR (head-to-head) and UAS-dref-IR (tail-to-tail), respectively. Phenotypes of the established transgenic fly lines crossed with GMR-GAL4 or en-GAL4 driver strain are summarized in Table 1 and those of the transgenic line 15 crossed with 25 different GAL4 lines are summarized in Table 2. Over-expression of dref-IR with Cg-GAL4 driver caused the generation of melanotic tumours in larvae, and flies died at a larval stage (Fig. 1B, Table 2). The Cg-GAL4 driver strain expresses GAL4 in blood cells (Asha et al. 2003). As noted previously, over-expression of DREF with the Cg-GAL4 driver also caused the generation of similar melanotic tumours in larvae and flies died at a larval stage (Fig. 1A) (Yoshida et al. 2001). UAS-dref-IR/+; +; 32B-GAL4/+, UAS-dref-IR/+; Act25-GAL4/+, UAS-dref-IR/+; +; Act5C-GAL4/+ and UAS-dref-IR/+; T80-GAL4/+ were larval or pupal lethal and UAS-dref-IR/+; +; dpp-GAL4/+, UAS-dref-IR/3735-GAL4 died during development (Table 2). In the UAS-dref-IR/GMR-GAL4 case, adult flies showed a rough eye phenotype (Tables 1 and 2, Fig. 2B,F). Flies carrying UAS-dref-IR/+; en-GAL4/+ died at an embryonic stage (Tables 1 and 2). However, when the transgenic line 10 was used, the wings were notched and the wing vein of L5 close to the distal margin was lost (Tables 1 and 2, Fig. 3C,D). We therefore used the transgenic line 10 in the analyses of the wing phenotype as described below.
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DREF is required for wing vein development by regulating the D-raf gene expression
In UAS-dref-IR/+; en-GAL4/+, there is a loss of veins in the L5 proximity (Fig. 3C,D), observed in 35% of the flies. Moreover, over-expression of DREF with the en-GAL4 driver caused ectopic vein development in the distal end of L5 (Yoshida et al. 2001) (Fig. 3E,F). These data suggest that DREF positively regulates formation of at least some proportion of L5 veins. Activation of EGFR signalling is essential for the development of all veins, as revealed by vein truncation phenotypes associated with viable Egfrtorpedo alleles and vein deletion within clones homozygous for strong hypomorphic Egfr alleles (Diaz-Benjumea & Garcia-Bellido 1990). D-raf is well known as a major component of the EGFR signalling pathway (Clifford & Schupbach 1992; Raz & Shilo 1992, 1993; Diaz-Benjumea & Hafen 1994; Scholz et al. 1997; Greenwood & Struhl 1999; Halfar et al. 2001; Radke et al. 2001; Yang & Baker 2001). It is reported that introduction of a mutation into the DRE-like sequence of the D-raf gene promoter results in reduction of D-raf gene promoter activity (Ryu et al. 1997), indicating that the DRE-like sequence is required for D-raf gene promoter activity. We carried out immunostaining with anti-DREF antibody against salivary gland polytene chromosomes in third-instar larvae and detected signals for DREF at the D-raf gene locus, 3A-1, on the X chromosome (Fig. 4A), suggesting that DREF binds to the genomic region containing the D-raf gene promoter. To determine whether DREF truly regulates expression of the D-raf gene, we examined effects of over-expression of dsRNA of the DREF gene on the D-raf gene promoter activity in cultured S2 cells. Northern blot analysis of the levels of DREF and D-raf transcripts in S2 cells treated with either dsRNA of the DREF gene or that of the LacZ gene revealed levels of DREF and D-raf transcripts to be reduced to 20% and 70%, respectively, with 10 µg of dsRNA of the DREF gene (Fig. 4B). In contrast, no reduction of levels of DREF and D-raf transcripts was observed in cells transfected with dsRNA of the LacZ gene (Fig. 4B). Under these conditions, activity of the D-raf gene promoter was reduced to 7% (Fig. 4C). The results indicate that DREF is required for the D-raf gene promoter activity in S2 cells.
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Over-expression of DREF activates EGFR signalling pathway during wing development
Although DREF enhances expression of the D-raf gene, this does not necessarily mean that DREF can activate the EGFR signalling pathway that is mediated by the phosphorylation cascade of its components. To gain further insight into this point, the phosphorylation state of the MAPK, a downstream component of the EGFR signalling pathway, was examined. In the third-instar wing imaginal disc, the activated form of MAPK, detected with antibodies that recognize diphospho-ERK (dp-ERK) (Gabay et al. 1997), showed a prominent localization along the veins in the wing pouch [Fig. 5A,C; see also (Gabay et al. 1997)]. In the posterior regions of wings from the DREF over-expressing flies, a broadening of dp-ERK expression on vein territories was evident (Fig. 5B,D), indicative of ectopic activation of the EGFR signalling pathway in wing imaginal discs.
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Discussion |
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The present study showed that over-expression of DREF protein or dref-IR with the en-GAL4 driver results in increasing width or loss, respectively, of the L5 vein close to the wing margin. The positive regulation appears because of enhanced D-raf gene expression (Fig. 6). From searches for DRE-like sequences in the Drosophila genome data base, genes for most components of EGFR signalling pathway, such as Ras85D, D-raf, Dsor1 (downstream of raf 1), a Drosophila homologue of mammalian MEK (Tsuda et al. 1993) contain multiple such elements in their 5'-flanking regions (M. Yoo, personal communication). Moreover, chromatin immunoprecipitation assays using anti-DREF antibody have provided evidence of specific binding of DREF to the genomic region containing the Ras85D gene promoter in vivo (data not shown). Taking the available information into account, we propose that DREF positively regulates genes for most of components of EGFR signalling pathway and consequently has an activating function. It has been revealed that activation of EGFR signalling induces the expression of rhomboid (rho) gene, which is one of the EGFR signalling target genes, and that rho protein promotes production of a secreted form of the EGFR ligand Spitz (sSpi) (Schweitzer et al. 1995; Golembo et al. 1996; Pickup & Banerjee 1999). One explanation of the non-cell autonomous EGFR signalling activation by DREF shown in Fig. 5 is that sSpi would diffuse and spatially propagate EGFR signalling beyond the region of DREF over-expression. In addition to EGFR signalling, previous studies noted that Notch and dpp are also involved in wing vein formation. As L5 wing vein phenotype is also similar to a reduced Notch signalling phenotype, we cannot rule out the possibility that Notch signalling is also regulated by DREF. Although further analyses are necessary to clarify this point, the possibility may be not likely, as no DRE sequence was found in the 5'-flanking 1-kb regions of genes involved in the Notch signalling pathway, such as Notch, Su(H), H, Fringe, O-FUT1, Delta and Serrate.
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Experimental procedures |
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A 1-kb DNA fragment containing the N-terminal region of DREF was isolated from the pBS II-DgDREF by digestion with ClaI and EcoRI and inserted into the SmaI and EcoRI sites of pBluscriptII SK(–) to create pBSII-DREF/SmaI/EcoRI. Then, the 1-kb fragment was isolated by digestion with BamHI and EcoRI and inserted into the EcoRI and BglII sites of pUAST to create pUAST-DREFTH. A 750-bp DNA fragment containing the N-terminal region of DREF was isolated from the pBSII–DcDREF by digestion with NotI and XhoI and then inserted into NotI and XhoI sites of pUAST-DREFTH to create pUAS-dref-IR (head-to-head) that can produce dref-IR. The pUAS-dref-IR (tail-to-tail) was created in a similar way.
Fly stocks
Fly stocks were cultured at 25 °C on standard food. The Canton S fly was used as the wild-type strain. The engraileD-GAL4 (en-GAL4) fly stock was kindly provided by Dr N. Dyson while the D-rafE1 fly stocks were generous gifts of Dr Y. Nishida. The Act25-GAL4 fly stock was kindly provided by Dr T. Todo. Establishment of the lines carrying GMR-GAL4 was described earlier (Robertson et al. 1988; Takahashi et al. 1999). All other stocks used in this study were obtained from the Bloomington Drosophila stock centre.
Establishment of the transgenic flies
P-element-mediated germ line transformation was carried out as described earlier (Spradling 1986). F1 transformants were selected on the basis of white eye colour rescue (Robertson et al. 1988). Seven and 10 independent lines were established for the pUAS-dref-IR (head-to-head) and pUAS-dref-IR (tail-to-tail), respectively. We used lines 10 and 15 carrying UAS-dref-IR (head-to-head) on the X chromosome in the detailed studies. Established transgenic strains carrying UAS-dref-IR constructs and their chromosomal linkages are listed in Table 1.
Over-expression experiments
Transgenic lines carrying UAS-dref-IR were crossed with several GAL4 driver lines and reared at 28 °C. The vein of increased width phenotype in UAS-DREF; en-GAL4/CyO stock was observed in flies reared at both 28 °C and 20 °C.
Immunohistochemistry
Third-instar larvae were dissected in Drosophila Ringer's solution and imaginal discs were fixed in 4% paraformaldehyde/phosphate-buffered saline (PBS) for 30 min at room temperature. After washing with PBS/0.3% Triton X-100 (PBS-T), the samples were blocked with PBS-T containing 10% normal goat serum for 20 min at room temperature (25 °C) and incubated with an anti-DREF monoclonal antibody (Hirose et al. 1996) at a 1 : 50 dilution, and anti-diphospho-ERK (dp-ERK) monoclonal antibody (Sigma) at a 1 : 200 dilution at 4 °C for 16 h. After extensive washing with PBS-T, the imaginal discs were incubated with an anti-mouse IgG conjugated with Alexa 488 (Molecular Probes, Eugene, OR) at a 1 : 400 dilution for 2 h at room temperature (25 °C). After extensive washing with PBS-T and PBS, samples were mounted in Fluoroguard Antifade Reagent (Bio-Rad Laboratories, Hercules, CA) for microscopic observation.
Immunostaining of polytene chromosomes
Polytene chromosomes spreads were made according to the protocol of Zink et al. (1991) from Canton S wild-type wandering third-instar larvae. Squashes were stored in PBS-0.05% Tween 20-1% bovine serum albumin (BSA) at 4 °C overnight and then incubated with anti-DREF monoclonal antibody at a 1 : 1000 dilution at 4 °C for 16 h. After extensive washing with PBS-0.05% Tween 20-1% BSA, samples were incubated at room temperature (25 °C) for 1 h with anti-mouse IgG conjugated with Alexa 594 (Molecular Probe) at a 1 : 400 dilution. The chromosomes were then washed with PBS-0.05% Tween 20-1% BSA and mounted in Fluoroguard Antifade Reagent (Bio-Rad Laboratories) for microscopic observation.
Western immunoblot hybridization analysis
Adults of the line carrying Act25-GAL4 transgene and line carrying UAS-dref-IR and Act25-GAL4 transgenes were frozen in liquid nitrogen and homogenized in a solution containing 50 mM Tris-Borate (pH 7.6), 400 mM KCl, 0.1% Triton X-100, 1 mM dithiothreitol, 0.1 mM EDTA, 1 mM phenylmethylsulphonyl fluoride, 10 µg each of aprotinin and leupeptin per ml, and 1 µg each of pepstatin, chymostatin and phosphoramidon per ml at various times after heat shock. Homogenates were centrifuged at 13 000 g
. at 4 °C for 5 min and extracts (60 µg of protein) were electrophoretically separated on SDS-10% polyacrylamide gels and transferred to polyvinylidene difluoride membranes (Bio-Rad Laboratories) in a solution containing 25 mM Tris-HCl (pH 9.5) and 20% methanol for 45 min at room temperature (25 °C). Blotted membranes were blocked with Tris-buffered saline (TBS) solution (50 mM Tris-HCl, pH 8.3 and 150 mM NaCl) containing 10% skim milk for 1 h at room temperature and then incubated with an anti-DREF monoclonal antibody (Hirose et al. 1996) at a 1 : 2000 dilution, or anti- tubulin monoclonal antibody (Sigma) at a 1 : 2000 dilution at 4 °C for 16 h. After washing with TBS, the blots were incubated with a horseradish peroxidase-labelled anti-mouse IgG (Amersham Pharmacia Biotech, Piscataway, NJ) at a 1 : 1500 dilution for 1 h at room temperature. Detection was performed with ECL Western blotting detection reagents (Amersham Pharmacia Biotech).
Northern blot hybridization analysis
Total cellular RNA was isolated from cultured S2 cells by the guanidium thiocyanate-phenol-chloroform extraction method and 20 µg aliquots were separated on 1% agarose gels containing formaldehyde and blotted onto sheets of GeneScreen Plus membrane (DuPont–NEN, Boston, MA). Probes were radiolabelled using the random primer method (Feinberg & Vogelstein 1983). Hybridization and washing conditions were the same as described elsewhere (Hirose et al. 1991). Blots were used to expose Kodak X-Omat XAR films. Quantification was with a BAS2500 (Fuji Film) imaging analyser. Ribosomal protein 49 (RP49) was used as an internal control.
Cell culture, transfection and luciferase assays
Drosophila S2 cells were grown at 25 °C in M3 (BF) medium (Cross & Sang 1978) supplemented with 10% foetal calf serum. For RNA interference experiments, 1 x 105 S2 cells were plated in 24-well dishes and transfected with DREF dsRNA or LacZ dsRNA with the aid of Cell-Fectin reagent (Life Technologies, Rockville, MD) as previously described (Kwon et al. 2003). At 24 h after dsRNA transfection, 50 ng of luciferase reporter plasmid was transfected into cells with the aid of Cell-Fectin reagent. Cells were harvested 48 h after transfection and the luciferase assay was carried out as previously described (Yamaguchi et al. 1994) using the Dual-Luciferase Reporter Assay System (Promega). Values were normalized to Renilla luciferase activity. All transient expression data reported in this paper represent the means from three independent experiments, each performed in triplicate.
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Acknowledgements |
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Footnotes |
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Present addresses:aLaboratory of Cell Biology, Department of Bioinformatics, Faculty of Engineering, Soka University, 1-236 Tangi-cho, Hachioji, Tokyo 192-8577, Japan;
bLaboratory of Molecular Oncology, MGH Cancer Center Building 149, 13th Street, Charlestown, MA 02129-2000, USA;
cDepartment of Life Science, Graduate School of Science, Himeji Institute of Technology, 3-2-1 Koto, Kamigori, Hyogo 678-1297, Japan.
* Correspondence: Email: myamaguc{at}kit.ac.jp |
References |
|---|
|
TopAbstractIntroductionResultsDiscussionExperimental proceduresReferences |
|---|
Brand, A.H. & Perrimon, N. (1993) Targeted gene expression as means of altering cell fates and generating dominant phenotypes. Development 118, 401–415.[Abstract]
Clifford, R.J. & Schupbach, T. (1992) The torpedo (DER) receptor tyrosine kinase is required at multiple times during Drosophila embryogenesis. Development 115, 853–872.[Abstract]
Cross, D.P. & Sang, J.H. (1978) Cell culture of individual Drosophila embryos. I. Development of wild type cultures. J. Embryol. Exp. Morph. 45, 161–172.[Medline]
Diaz-Benjumea, F.J. & Garcia-Bellido, A. (1990) Behaviour of cells mutant for an EGF receptor homologue of Drosophila in genetic mosaics. Proc. R. Soc. Lond. B Biol. Sci. 242, 36–44.[Medline]
Diaz-Benjumea, F.J. & Hafen, E. (1994) The sevenless signalling cassette mediates Drosophila EGF receptor function during epidermal development. Development 120, 569–578.[Abstract]
Duronio, R.J., O’Farrell, P.H., Xie, J.E., Brook, A. & Dyson, N. (1995) The transcription factor E2F is required for S phase during Drosophila embryogenesis. Genes Dev.
9, 1445–1455.
Feinberg, A.P. & Vogelstein, B. (1983) A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal. Biochem. 132, 6–13.[CrossRef][Medline]
Gabay, L., Seger, R. & Shilo, B.Z. (1997)
In situ activation pattern of Drosophila EGF receptor pathway during development. Science
277, 1103–1106.
Golembo, M., Raz, E. & Shilo, B.Z. (1996) The Drosophila embryonic midline is the site of Spitz processing, and induces activation of the EGF receptor in the ventral ectoderm. Development 122, 3363–3370.[Abstract]
Greenwood, S. & Struhl, G. (1999) Progression of the morphogenetic furrow in the Drosophila eye: the roles of hedgehog, decapentaplegic and the Raf pathway. Development 126, 5795–5808.[Abstract]
Halfar, K., Rommel, C., Stocker, H. & Hafen, E. (2001) Ras controls growth, survival and differentiation in the Drosophila eye by different thresholds of MAP kinase activity. Development 128, 1687–1696.[Abstract]
Hirose, F., Yamaguchi, M., Nishida, Y., et al. (1991) Structure and expression during development of Drosophila melanogaster gene for DNA polymerase . Nucl. Acids Res.
19, 4991–4998.
Hirose, F., Yamaguchi, M., Handa, H., Inomata, Y. & Matsukage, A. (1993) Novel 8-base pair sequence (Drosophila DNA replication-related element) and specific binding factor involved in the expression of Drosophila genes for DNA polymerase and proliferating cell nuclear antigen. J. Biol. Chem.
268, 2092–2099.
Hirose, F., Yamaguchi, M., Kuroda, K., et al. (1996) Isolation and characterization of cDNA for DREF, a promoter-activating factor for Drosophila DNA replication-related genes. J. Biol. Chem.
271, 3930–3937.
Hirose, F., Ohshima, N., Shiraki, M., et al. (2001) Ectopic expression of DREF induces DNA synthesis, apoptosis, and unusual morphogenesis in the Drsophila eye imaginal disc: possible interaction with Polycomb and trithorax group proteins. Mol. Cell. Biol.
21, 7231–7242.
Hirose, F., Ohshima, N., Kwon, E.J., et al. (2002)
Drosophila Mi-2 negatively regulates dDREF by inhibiting its DNA-binding activity. Mol. Cell. Biol.
22, 5182–5193.
Hochheimer, A., Zhou, S., Zheng, S., et al. (2002) TRF2 associates with DREF and directs promoter-selective gene expression in Drosophila . Nature 420, 439–445.[CrossRef][Medline]
Jasper, H., Benes, V., Atzberger, A., et al. (2002) A genomic switch at the transition from cell proliferation to terminal differentiation in the Drosophila eye. Dev. Cell 3, 511–521.[CrossRef][Medline]
Kennerdell, J.R. & Carthew, R.W. (1998) Use of ds-RNA-mediated genetic interference to demonstrate that frizzled and frizzled 2 act in the Wingless pathway. Cell 95, 1017–1026.[CrossRef][Medline]
Kwon, E.J., Seto, H., Hirose, F., et al. (2003) Transcription control of a gene for Drosophila transcription factor, DREF by DRE and cis-elements conserved between Drosophila melanogaster and virilis . Gene 309, 101–116.[CrossRef][Medline]
Matsukage, A., Hirose, F., Hayashi, Y., Hamada, K. & Yamaguchi, M. (1995) The DRE sequence TATCGATA, a putative promoter-activating element for Drosophila melanogaster cell-proliferation-related genes. Gene 166, 233–236.[CrossRef][Medline]
Misquitta, L. & Paterson, B.M. (1999) Targeted disruption of gene function in Drosophila by RNA interference (RNA-i): a role for nautilus in embryonic somatic muscle formation. Proc. Natl. Acad. Sci. USA
96, 1451–1456.
Ohler, U., Liao, G.C., Niemann, H. & Rubin, G.M. (2002) Computational analysis of core promoters in the Drosophila genome . Genome Biol. 3, 0081–0087.0012.
Ohno, K., Takahashi, T., Hirose, F., et al. (2000) Characterization of a Drosophila homologue of the human myelodysplasia/myeloid leukemia factor (MLF). Gene 260, 133–143.[CrossRef][Medline]
Pickup, A.T. & Banerjee, U. (1999) The role of star in the production of an activated ligand for the EGF receptor signaling pathway. Dev. Biol. 205, 254–259.[CrossRef][Medline]
Radke, K., Johnson, K., Guo, R., Davidson, A. & Ambrosio, L. (2001)
Drosophila-Raf acts to elabotate dorsoventral pattern in the ectoderm of developing embryos. Genetics
159, 1031–1044.
Raz, E. & Shilo, B.Z. (1992) Dissection of the faint little ball (flb) phenotype: determination of the development of Drosophila central nervous system by early interactions in the ectoderm. Development 114, 113–123.[Abstract]
Raz, E. & Shilo, B.Z. (1993) Establishment of ventral cell fates in the Drosophila embryonic ectoderm requires DER, the EGF receptor homolog. Genes Dev.
7, 1937–1948.
Robertson, H.M., Preston, C.R., Philips, R.W., et al. (1988) A stable genomic source of P-element transposase in Drosophila melanogaster
. Genetics
118, 461–470.
Ryu, J.R., Choi, T.Y., Kwon, E.J., et al. (1997) Transcriptional regulation of the Drosophila-raf proto-oncogene by the DNA replication-related element (DRE)/DRE-binding factor (DREF) system. Nucl. Acids Res.
25, 794–799.
Scholz, H., Sadlowski, E., Klaes, A. & Klambt, C. (1997) Control of midline glia development in the embryonic Drosophila CNS. Mech. Dev. 64, 137–151.[CrossRef][Medline]
Schweitzer, R. & Shilo, B.Z. (1997) A thousand and one roles for the Drosophila EGF receptor. Trends Genet. 13, 191–196.[CrossRef][Medline]
Schweitzer, R., Shaharabany, M., Seger, R. & Shilo, B.Z. (1995) Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. Genes Dev.
9, 1518–1529.
Spradling, A.C. (1986) P-element-mediated transformation. In: Drosophila: a Practical Approach (ed. D.B. Roberts), pp. 175–197, Oxford: IRL Press.
Takahashi, Y., Hirose, F., Matsukage, A. & Yamaguchi, M. (1999) Identification of three conserved regions in the DREF transcription factors from Drosophila melanogaster and Drosophila virilis
. Nucl. Acids Res.
27, 510–516.
Tsuda, L., Inoue, Y.H., Yoo, M.A., et al. (1993) A protein kinase similar to MAP kinase activator acts downstream of the raf kinase in Drosophila . Cell 72, 407–414.[CrossRef][Medline]
Yamaguchi, M., Hayashi, Y., Matsuoka, S., Takahashi, T. & Matsukage, A. (1994) Differential effect of p53 on the promoters of mouse DNA polymerase ß gene and proliferating-cell-nuclear-antigen gene. Eur. J. Biochem. 221, 227–237.[Medline]
Yamaguchi, M., Hayashi, Y. & Matsukage, A. (1995a) Essential role of E2F recognition sites in regulation of the proliferating cell nuclear antigen gene promoter during Drosophila development. J. Biol. Chem.
270, 25159–25165.
Yamaguchi, M., Hayashi, Y., Nishimoto, Y., et al. (1995b) A nucleotide sequence essential for the function of DRE, a common promoter element for Drosophila DNA replication-related genes. J. Biol. Chem.
270, 15808–15814.
Yamaguchi, M., Hirose, F. & Matsukage, A. (1996) Roles of multiple promoter elements of the proliferating cell nuclear antigen gene during Drosophila development. Genes Cells 1, 47–58.[Abstract]
Yang, L. & Baker, N.E. (2001) Role of the EGFR/Ras/Raf pathway in specification of photoreceptor cells in the Drosophila retina. Development 128, 1183–1191.[Abstract]
Yoneda-Kato, N., Look, A.T., Kirstein, M.N., et al. (1996) The t(3, 5) (q25.1,q34) of myelodysplastic syndrome and acute myeloid leukemia produces a novel fusion gene, NPM-MLF1. Oncogene 12, 265–275.[Medline]
Yoshida, H., Inoue, Y.H., Hirose, F., et al. (2001) Over-expression of DREF in the Drosophila wing imaginal disc induces apoptosis and a notching wing phenotype. Genes Cells 6, 877–886.[Abstract]
Zink, B., Engstrom, Y., Gehring, W.J. & Paro, R. (1991) Direct interaction of the Polycomb protein with Antennapedia regulatory sequences in polytene chromosomes of Drosophila melanogaster . EMBO J. 10, 153–162.[Medline]
Received: 2 June 2004
Accepted: 6 July 2004
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Y. S. Kim, M. J. Shin, D. J. Yang, M. Yamaguchi, S. Y. Park, and M. A. Yoo Transcriptional regulation of the Drosophila ANT gene by the DRE/DREF system Genes Cells, May 1, 2007; 12(5): 569 - 579. [Abstract] [Full Text] [PDF]
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 D. Yamashita, Y. Sano, Y. Adachi, Y. Okamoto, H. Osada, T. Takahashi, T. Yamaguchi, T. Osumi, and F. Hirose hDREF Regulates Cell Proliferation and Expression of Ribosomal Protein Genes Mol. Cell. Biol., March 15, 2007; 27(6): 2003 - 2013. [Abstract] [Full Text] [PDF]
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 F. C. Gonsalves and D. A. Weisblat MAPK regulation of maternal and zygotic Notch transcript stability in early development PNAS, January 9, 2007; 104(2): 531 - 536. [Abstract] [Full Text] [PDF]
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S. Martin-Lanneree, C. Lasbleiz, M. Sanial, S. Fouix, F. Besse, H. Tricoire, and A. Plessis Characterization of the Drosophila myeloid leukemia factor Genes Cells, December 1, 2006; 11(12): 1317 - 1335. [Abstract] [Full Text] [PDF]
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J. Hyun, H. Jasper, and D. Bohmann DREF Is Required for Efficient Growth and Cell Cycle Progression in Drosophila Imaginal Discs Mol. Cell. Biol., July 1, 2005; 25(13): 5590 - 5598. [Abstract] [Full Text] [PDF]
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