Home LiteratureArticle Details
PMID: 9383058 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Dominant enhancers of Egfr in Drosophila melanogaster: genetic links between the Notch and Egfr signaling pathways.

Genetics ·Vol. 147 ·No. 3 ·1997-11-00 ·Pages 1139-53

Price JV, Savenye ED, Lum D, Breitkreutz A

Abstract

The Drosophila epidermal growth factor receptor (EGFR) is a key component of a complex signaling pathway that participates in multiple developmental processes. We have performed an F1 screen for mutations that cause dominant enhancement of wing vein phenotypes associated with mutations in Egfr. With this screen, we have recovered mutations in Hairless (H), vein, groucho (gro), and three apparently novel loci. All of the E(Egfr)s we have identified show dominant interactions in transheterozygous combinations with each other and with alleles of N or Su(H), suggesting that they are involved in cross-talk between the N and EGFR signaling pathways. Further examination of the phenotypic interactions between Egfr, H, and gro revealed that reductions in Egfr activity enhanced both the bristle loss associated with H mutations, and the bristle hyperplasia and ocellar hypertrophy associated with gro mutations. Double mutant combinations of Egfr and gro hypomorphic alleles led to the formation of ectopic compound eyes in a dosage sensitive manner. Our findings suggest that these E(Egfr)s represent links between the Egfr and Notch signaling pathways, and that Egfr activity can either promote or suppress Notch signaling, depending on its developmental context.

MeSH Terms
Animals Calcium-Calmodulin-Dependent Protein Kinases/genetics,metabolism Chromosome Mapping Drosophila Proteins Drosophila melanogaster/genetics Enhancer Elements, Genetic ErbB Receptors/genetics,metabolism Extracellular Signal-Regulated MAP Kinases Heterozygote Insect Proteins/genetics,metabolism Membrane Proteins/metabolism Mutagenesis Phenotype Receptors, Notch Repressor Proteins/genetics,metabolism Signal Transduction Wings, Animal/growth & development
Chemicals
Drosophila Proteins Insect Proteins Membrane Proteins N protein, Drosophila Receptors, Notch Repressor Proteins Su(H) protein, Drosophila ErbB Receptors Calcium-Calmodulin-Dependent Protein Kinases Extracellular Signal-Regulated MAP Kinases rl protein, Drosophila
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Price J V
Institute of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada. jprice@sfu.ca
Savenye E D
Lum D
Breitkreutz A
References (64)
64 references, click to expand
  1. Role of transactivation of the EGF receptor in signalling by G-protein-coupled receptors.
    Nature. 1996 Feb 8;379(6565):557-60 PMID: 8596637
  2. Polarization of both major body axes in Drosophila by gurken-torpedo signalling.
    Nature. 1995 Jun 22;375(6533):654-8 PMID: 7791898
  3. The torpedo (DER) receptor tyrosine kinase is required at multiple times during Drosophila embryogenesis.
    Development. 1992 Jul;115(3):853-72 PMID: 1425358
  4. Complex function and expression of Delta during Drosophila oogenesis.
    Genetics. 1993 Apr;133(4):967-78 PMID: 8462854
  5. Temperature-sensitive periods and autonomy of pleiotropic effects of l(1)Nts1, a conditional notch lethal in Drosophila.
    Dev Biol. 1978 Feb;62(2):432-46 PMID: 414945
  6. Signal transduction in the early Drosophila embryo: when genetics meets biochemistry.
    Trends Biochem Sci. 1994 Nov;19(11):509-13 PMID: 7855897
  7. A perfect vulva every time: gradients and signaling cascades in C. elegans.
    Cell. 1995 Jul 28;82(2):171-4 PMID: 7628006
  8. The spitz gene is required for photoreceptor determination in the Drosophila eye where it interacts with the EGF receptor.
    Mech Dev. 1994 Oct;48(1):25-33 PMID: 7833286
  9. Torso, a receptor tyrosine kinase required for embryonic pattern formation, shares substrates with the sevenless and EGF-R pathways in Drosophila.
    Genes Dev. 1993 Apr;7(4):633-46 PMID: 8384582
  10. Genetic analysis of enhancer of split, a locus involved in neurogenesis in Drosophila melanogaster.
    Genetics. 1988 May;119(1):63-74 PMID: 17246426
  11. Vein is a novel component in the Drosophila epidermal growth factor receptor pathway with similarity to the neuregulins.
    Genes Dev. 1996 Sep 15;10(18):2302-13 PMID: 8824589
  12. canoe encodes a novel protein containing a GLGF/DHR motif and functions with Notch and scabrous in common developmental pathways in Drosophila.
    Genes Dev. 1995 Mar 1;9(5):612-25 PMID: 7698650
  13. Coordinately and differentially mutable activities of torpedo, the Drosophila melanogaster homolog of the vertebrate EGF receptor gene.
    Genetics. 1989 Dec;123(4):771-87 PMID: 2515109
  14. Groucho is required for Drosophila neurogenesis, segmentation, and sex determination and interacts directly with hairy-related bHLH proteins.
    Cell. 1994 Dec 2;79(5):805-15 PMID: 8001118
  15. A protein kinase similar to MAP kinase activator acts downstream of the raf kinase in Drosophila.
    Cell. 1993 Feb 12;72(3):407-14 PMID: 8381718
  16. Ras1 and a putative guanine nucleotide exchange factor perform crucial steps in signaling by the sevenless protein tyrosine kinase.
    Cell. 1991 Nov 15;67(4):701-16 PMID: 1934068
  17. A temperature-sensitive MEK mutation demonstrates the conservation of the signaling pathways activated by receptor tyrosine kinases.
    Genes Dev. 1994 Sep 15;8(18):2176-87 PMID: 7958887
  18. Analysis of dominant enhancers and suppressors of activated Notch in Drosophila.
    Genetics. 1996 Nov;144(3):1127-41 PMID: 8913755
  19. Differential requirement for EGF-like ligands in Drosophila wing development.
    Mech Dev. 1997 Feb;62(1):41-50 PMID: 9106165
  20. Spatially localized rhomboid is required for establishment of the dorsal-ventral axis in Drosophila oogenesis.
    Cell. 1993 Jun 4;73(5):953-65 PMID: 8500182
  21. Expression and function of decapentaplegic and thick veins during the differentiation of the veins in the Drosophila wing.
    Development. 1997 Mar;124(5):1007-18 PMID: 9056776
  22. sur-2, a novel gene, functions late in the let-60 ras-mediated signaling pathway during Caenorhabditis elegans vulval induction.
    Genes Dev. 1995 Sep 15;9(18):2251-65 PMID: 7557379
  23. Functional relationships between Notch, Su(H) and the bHLH genes of the E(spl) complex: the E(spl) genes mediate only a subset of Notch activities during imaginal development.
    Development. 1996 Sep;122(9):2719-28 PMID: 8787746
  24. groucho and hedgehog regulate engrailed expression in the anterior compartment of the Drosophila wing.
    Development. 1995 Oct;121(10):3467-76 PMID: 7588079
  25. Ras pathways in Caenorhabditis elegans.
    Curr Opin Genet Dev. 1995 Feb;5(1):38-43 PMID: 7749323
  26. Inhibition of the DNA-binding activity of Drosophila suppressor of hairless and of its human homolog, KBF2/RBP-J kappa, by direct protein-protein interaction with Drosophila hairless.
    Genes Dev. 1994 Oct 15;8(20):2491-503 PMID: 7958912
  27. Two closely linked mutations in Drosophila melanogaster that are lethal to opposite sexes and interact with daughterless.
    Genetics. 1978 Dec;90(4):683-98 PMID: 105964
  28. Suppressor of hairless directly activates transcription of enhancer of split complex genes in response to Notch receptor activity.
    Genes Dev. 1995 Nov 1;9(21):2609-22 PMID: 7590239
  29. Cell determination strategies in the Drosophila eye.
    Development. 1997 Jan;124(2):261-70 PMID: 9053303
  30. Genetic and molecular analyses of mutations involved in Drosophila raf signal transduction.
    EMBO J. 1994 Jun 1;13(11):2592-9 PMID: 8013459
  31. Analysis of genetic mosaics in developing and adult Drosophila tissues.
    Development. 1993 Apr;117(4):1223-37 PMID: 8404527
  32. The involvement of the Notch locus in Drosophila oogenesis.
    Development. 1992 Aug;115(4):913-22 PMID: 1451667
  33. Affinity for the nuclear compartment and expression during cell differentiation implicate phosphorylated Groucho/TLE1 forms of higher molecular mass in nuclear functions.
    Biochem J. 1996 Jul 15;317 ( Pt 2):523-31 PMID: 8713081
  34. Genetic Analysis of the Hairy Locus in DROSOPHILA MELANOGASTER.
    Genetics. 1985 Nov;111(3):463-86 PMID: 17246301
  35. The neurogenic suppressor of hairless DNA-binding protein mediates the transcriptional activation of the enhancer of split complex genes triggered by Notch signaling.
    Genes Dev. 1995 Nov 1;9(21):2598-608 PMID: 7590238
  36. Genes of the Enhancer of split and achaete-scute complexes are required for a regulatory loop between Notch and Delta during lateral signalling in Drosophila.
    Development. 1996 Jan;122(1):161-71 PMID: 8565827
  37. The molecular genetics of Enhancer of split, a gene required for embryonic neural development in Drosophila.
    EMBO J. 1988 Dec 1;7(12):3917-27 PMID: 3145200
  38. A gain-of-function mutation in Drosophila MAP kinase activates multiple receptor tyrosine kinase signaling pathways.
    Cell. 1994 Mar 11;76(5):875-88 PMID: 8124723
  39. Effect on eye development of dominant mutations in Drosophila homologue of the EGF receptor.
    Nature. 1989 Jul 13;340(6229):150-3 PMID: 2500601
  40. The Drosophila rhomboid gene mediates the localized formation of wing veins and interacts genetically with components of the EGF-R signaling pathway.
    Genes Dev. 1993 Jun;7(6):961-73 PMID: 8504935
  41. The neurogenic locus brainiac cooperates with the Drosophila EGF receptor to establish the ovarian follicle and to determine its dorsal-ventral polarity.
    Development. 1992 Sep;116(1):177-92 PMID: 1483386
  42. Signal transduction and the fate of the R7 photoreceptor in Drosophila.
    Trends Genet. 1991 Nov-Dec;7(11-12):372-7 PMID: 1668189
  43. A thousand and one roles for the Drosophila EGF receptor.
    Trends Genet. 1997 May;13(5):191-6 PMID: 9154002
  44. Down-regulation of Drosophila Egf-r mRNA levels following hyperactivated receptor signaling.
    Development. 1994 Sep;120(9):2593-600 PMID: 7956834
  45. The Drosophila dorsoventral patterning gene gurken produces a dorsally localized RNA and encodes a TGF alpha-like protein.
    Cell. 1993 Oct 8;75(1):165-74 PMID: 7691414
  46. Genetic dissection of a neurodevelopmental pathway: Son of sevenless functions downstream of the sevenless and EGF receptor tyrosine kinases.
    Cell. 1991 Jan 11;64(1):39-48 PMID: 1846090
  47. lin-25, a gene required for vulval induction in Caenorhabditis elegans.
    Genes Dev. 1995 Feb 1;9(3):341-57 PMID: 7867931
  48. Hairless promotes stable commitment to the sensory organ precursor cell fate by negatively regulating the activity of the Notch signaling pathway.
    Dev Biol. 1995 Dec;172(2):479-94 PMID: 8612965
  49. The sevenless signalling cassette mediates Drosophila EGF receptor function during epidermal development.
    Development. 1994 Mar;120(3):569-78 PMID: 8162856
  50. Analysis of the genetic hierarchy guiding wing vein development in Drosophila.
    Development. 1995 Mar;121(3):785-801 PMID: 7720583
  51. cornichon and the EGF receptor signaling process are necessary for both anterior-posterior and dorsal-ventral pattern formation in Drosophila.
    Cell. 1995 Jun 16;81(6):967-78 PMID: 7540118
  52. Role of neurogenic genes in establishment of follicle cell fate and oocyte polarity during oogenesis in Drosophila.
    Cell. 1991 Aug 9;66(3):433-49 PMID: 1907889
  53. The torso receptor protein-tyrosine kinase signaling pathway: an endless story.
    Cell. 1993 Jul 30;74(2):219-22 PMID: 8343949
  54. The torso pathway in Drosophila: lessons on receptor tyrosine kinase signaling and pattern formation.
    Dev Biol. 1994 Dec;166(2):380-95 PMID: 7813764
  55. let-60, a gene that specifies cell fates during C. elegans vulval induction, encodes a ras protein.
    Cell. 1990 Nov 30;63(5):921-31 PMID: 2257629
  56. Hairless is required for the development of adult sensory organ precursor cells in Drosophila.
    Development. 1991 Jan;111(1):89-104 PMID: 2015800
  57. The Drosophila TGF alpha homolog Spitz acts in photoreceptor recruitment in the developing retina.
    Development. 1997 Jan;124(2):343-51 PMID: 9053310
  58. Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination.
    Genes Dev. 1995 Jun 15;9(12):1518-29 PMID: 7601354
  59. Reiterative use of the EGF receptor triggers differentiation of all cell types in the Drosophila eye.
    Cell. 1996 Nov 15;87(4):651-60 PMID: 8929534
  60. The Enhancer of split complex and adjacent genes in the 96F region of Drosophila melanogaster are required for segregation of neural and epidermal progenitor cells.
    Genetics. 1992 Oct;132(2):481-503 PMID: 1427039
  61. The Drosophila spitz gene encodes a putative EGF-like growth factor involved in dorsal-ventral axis formation and neurogenesis.
    Genes Dev. 1992 Aug;6(8):1503-17 PMID: 1644292
  62. Identification of AF-6 and canoe as putative targets for Ras.
    J Biol Chem. 1996 Jan 12;271(2):607-10 PMID: 8557659
  63. Establishment of ventral cell fates in the Drosophila embryonic ectoderm requires DER, the EGF receptor homolog.
    Genes Dev. 1993 Oct;7(10):1937-48 PMID: 8406000
  64. A screen for genes that function downstream of Ras1 during Drosophila eye development.
    Genetics. 1996 May;143(1):315-29 PMID: 8722784
Article Info
Journal
Genetics
Abbr.
Genetics
ISSN
0016-6731
Published
1997-11-00
Pages
1139-53
Language
English
Region
United States
NLM ID
0374636
PMCID
PMC1208239
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com