A mosaic analysis in Drosophila fat body cells of the control of antimicrobial peptide genes by the Rel proteins Dorsal and DIF

Expression of the gene encoding the antifungal peptide Drosomycin in Drosophila adults is controlled by the Toll signaling pathway. The Rel proteins Dorsal and DIF (Dorsal‐related immunity factor) are possible candidates for the transactivating protein in the Toll pathway that directly regulates the drosomycin gene. We have examined the requirement of Dorsal and DIF for drosomycin expression in larval fat body cells, the predominant immune‐responsive tissue, using the yeast site‐specific flp/FRT recombination system to generate cell clones homozygous for a deficiency uncovering both the dorsal and the dif genes. Here we show that in the absence of both genes, the immune‐inducibility of drosomycin is lost but can be rescued by overexpression of either dorsal or dif under the control of a heat‐shock promoter. This result suggests a functional redundancy between both Rel proteins in the control of drosomycin gene expression in the larvae of Drosophila. Interestingly, the gene encoding the antibacterial peptide Diptericin remains fully inducible in the absence of the dorsal and dif genes. Finally, we have used fat body cell clones homozygous for various mutations to show that a linear activation cascade Spaetzle→ Toll→Cactus→Dorsal/DIF leads to the induction of the drosomycin gene in larval fat body cells.

[1]  P. Georgel,et al.  Dorsal-B, a splice variant of the Drosophila factor Dorsal, is a novel Rel/NF-kappaB transcriptional activator. , 1999, Gene.

[2]  L. Stevens,et al.  The Dorsal-related immunity factor (Dif) can define the dorsal-ventral axis of polarity in the Drosophila embryo. , 1998, Development.

[3]  S. Govind,et al.  A role for the Drosophila Toll/Cactus pathway in larval hematopoiesis. , 1998, Development.

[4]  B. Lemaître,et al.  In Vivo Regulation of the IκB Homologuecactus during the Immune Response ofDrosophila * , 1998, The Journal of Biological Chemistry.

[5]  K. Anderson,et al.  Regulated nuclear import of Rel proteins in the Drosophila immune response , 1998, Nature.

[6]  B. Lemaître,et al.  A drosomycin–GFP reporter transgene reveals a local immune response in Drosophila that is not dependent on the Toll pathway , 1998, The EMBO journal.

[7]  R. Reuter,et al.  The genetic control of the distinction between fat body and gonadal mesoderm in Drosophila. , 1998, Development.

[8]  B. Lemaître,et al.  Drosophila host defense: differential induction of antimicrobial peptide genes after infection by various classes of microorganisms. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Antony Rodriguez,et al.  The 18‐wheeler mutation reveals complex antibacterial gene regulation in Drosophila host defense , 1997, The EMBO journal.

[10]  A. Chiba,et al.  Toll, a muscle cell surface molecule, locally inhibits synaptic initiation of the RP3 motoneuron growth cone in Drosophila. , 1997, Development.

[11]  J. A. Hergannan,et al.  Drosophila immunity. , 1997, Trends in cell biology.

[12]  Robert Geisler,et al.  A gradient of cytoplasmic Cactus degradation establishes the nuclear localization gradient of the dorsal morphogen in Drosophila , 1996, Mechanisms of Development.

[13]  D. Hultmark,et al.  Origins of immunity: Relish, a compound Rel-like gene in the antibacterial defense of Drosophila. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[14]  P. Georgel,et al.  Drosophila immunity: a comparative analysis of the Rel proteins dorsal and Dif in the induction of the genes encoding diptericin and cecropin. , 1996, Nucleic acids research.

[15]  M. Gayle,et al.  T1/ST2 Signaling Establishes It as a Member of an Expanding Interleukin-1 Receptor Family (*) , 1996, The Journal of Biological Chemistry.

[16]  R. Steward,et al.  Regulated nuclear import of the Drosophila rel protein dorsal: structure-function analysis , 1996, Molecular and cellular biology.

[17]  M. Meister,et al.  Ecdysone and insect immunity: the maturation of the inducibility of the diptericin gene in Drosophila larvae. , 1996, Insect biochemistry and molecular biology.

[18]  K. Anderson,et al.  A conserved signaling pathway: the Drosophila toll-dorsal pathway. , 1996, Annual review of cell and developmental biology.

[19]  Interactions of a Rel protein with its inhibitor. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[20]  M. Meister,et al.  A recessive mutation, immune deficiency (imd), defines two distinct control pathways in the Drosophila host defense. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[21]  E. Levashina,et al.  Metchnikowin, a novel immune-inducible proline-rich peptide from Drosophila with antibacterial and antifungal properties. , 1995, European journal of biochemistry.

[22]  Y. Ip,et al.  The dorsal‐related immunity factor, Dif, is a sequence‐specific trans‐activator of Drosophila Cecropin gene expression. , 1995, The EMBO journal.

[23]  M. Levine,et al.  Specificity of Rel-inhibitor interactions in Drosophila embryos , 1995, Molecular and cellular biology.

[24]  D. Hoshizaki,et al.  Identification of fat-cell enhancer activity in Drosophila melanogaster using P-element enhancer traps. , 1995, Genome.

[25]  H. Keshishian,et al.  The Drosophila toll gene functions zygotically and is necessary for proper motoneuron and muscle development. , 1995, Developmental biology.

[26]  D. Hultmark,et al.  Identification of early genes in the Drosophila immune response by PCR-based differential display: the Attacin A gene and the evolution of attacin-like proteins. , 1995, Insect biochemistry and molecular biology.

[27]  R. Steward,et al.  Functional analysis and regulation of nuclear import of dorsal during the immune response in Drosophila. , 1995, The EMBO journal.

[28]  M. Meister,et al.  Insect immunity. A transgenic analysis in Drosophila defines several functional domains in the diptericin promoter. , 1994, The EMBO journal.

[29]  P. Fehlbaum,et al.  Insect immunity. Septic injury of Drosophila induces the synthesis of a potent antifungal peptide with sequence homology to plant antifungal peptides. , 1994, The Journal of biological chemistry.

[30]  R. Lanot,et al.  Characterization and transcriptional profiles of a Drosophila gene encoding an insect defensin. A study in insect immunity. , 1994, European journal of biochemistry.

[31]  M. Levine,et al.  Dif, a dorsal-related gene that mediates an immune response in Drosophila , 1993, Cell.

[32]  M. Meister,et al.  Expression and nuclear translocation of the rel/NF-kappa B-related morphogen dorsal during the immune response of Drosophila. , 1993, Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie.

[33]  D. Hultmark,et al.  kappa B-like motifs regulate the induction of immune genes in Drosophila. , 1993, Journal of molecular biology.

[34]  A. van Dorsselaer,et al.  A novel inducible antibacterial peptide of Drosophila carries an O-glycosylated substitution. , 1993, The Journal of biological chemistry.

[35]  G. Rubin,et al.  Analysis of genetic mosaics in developing and adult Drosophila tissues. , 1993, Development.

[36]  M. Meister,et al.  Insect immunity. Two 17 bp repeats nesting a kappa B‐related sequence confer inducibility to the diptericin gene and bind a polypeptide in bacteria‐challenged Drosophila. , 1993, The EMBO journal.

[37]  Konrad Basler,et al.  Organizing activity of wingless protein in Drosophila , 1993, Cell.

[38]  S. Kidd Characterization of the Drosophila cactus locus and analysis of interactions between cactus and dorsal proteins , 1992, Cell.

[39]  N. Perrimon,et al.  Use of a yeast site-specific recombinase to produce female germline chimeras in Drosophila. , 1992, Genetics.

[40]  D. Zachary,et al.  Insect immunity: developmental and inducible activity of the Drosophila diptericin promoter. , 1992, The EMBO journal.

[41]  D. Lindsley,et al.  The Genome of Drosophila Melanogaster , 1992 .

[42]  C. Nüsslein-Volhard,et al.  cactus, a maternal gene required for proper formation of the dorsoventral morphogen gradient in Drosophila embryos. , 1991, Development.

[43]  K. Golic Site-specific recombination between homologous chromosomes in Drosophila. , 1991, Science.

[44]  B. Lemaître,et al.  P regulatory products repress in vivo the P promoter activity in P-lacZ fusion genes. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[45]  S. Wasserman,et al.  Genetic and molecular characterization of tube, a Drosophila gene maternally required for embryonic dorsoventral polarity. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[46]  D. Hultmark,et al.  Insect immunity. Characterization of a Drosophila cDNA encoding a novel member of the diptericin family of immune peptides. , 1990, The Journal of biological chemistry.

[47]  D. Hultmark,et al.  The cecropin locus in Drosophila; a compact gene cluster involved in the response to infection. , 1990, The EMBO journal.

[48]  K. Anderson,et al.  Zygotic expression and activity of the Drosophila Toll gene, a gene required maternally for embryonic dorsal-ventral pattern formation. , 1988, Genetics.

[49]  R. Steward Dorsal, an embryonic polarity gene in Drosophila, is homologous to the vertebrate proto-oncogene, c-rel. , 1987, Science.

[50]  C. Nüsslein-Volhard,et al.  The genetics of the dorsal-Bicaudal-D region of Drosophila melanogaster. , 1986, Genetics.

[51]  K. Anderson,et al.  Establishment of dorsal-ventral polarity in the Drosophila embryo: Genetic studies on the role of the Toll gene product , 1985, Cell.

[52]  K. Anderson,et al.  Information for the dorsal–ventral pattern of the Drosophila embryo is stored as maternal mRNA , 1984, Nature.

[53]  P. O. O'Connell,et al.  Sequence, structure, and codon preference of the Drosophila ribosomal protein 49 gene , 1984, Nucleic Acids Res..