Advertisement
JOURNAL ARTICLES
The intracellular deletions of Delta and Serrate define dominant negative forms of the Drosophila Notch ligands
X. Sun, S. Artavanis-Tsakonas
Development 1996 122: 2465-2474;

Summary

We examined the function of the intracellular domains of the two known Drosophila Notch ligands, Delta and Serrate, by expressing wild-type and mutant forms in the developing Drosophila eye under the sevenless promoter. The expression of intracellularly truncated forms of either Delta (sev-DlTM) or Serrate (sev-SerTM) leads to extra photoreceptor phenotypes, similar to the eye phenotypes associated with loss-of-function mutations of either Notch or Delta. Consistent with the notion that the truncated ligands reduce. Notch signalling activity, the eye phenotypes of sev-DlTM and sev-SerTM are enhanced by loss-of-function mutations in the Notch pathway elements, Notch, Delta, mastermind, deltex and groucho, but are suppressed by a duplication of Delta or mutations in Hairless, a negative regulator of the pathway. These observations were extended to the molecular level by demonstrating that the expression of Enhancer of split m delta, a target of Notch signalling, is down-regulated by the truncated ligands highly expressed in neighbouring cells. We conclude that the truncated ligands act as antagonists of Notch signalling.

Reference

    1. Artavanis-Tsakonas S.,
    2. Matsuno K.,
    3. Fortini M. E.
    (1995) Notch signaling. Science 268, 225–232
    OpenUrlAbstract/FREE Full Text
    1. Baker N. E.,
    2. Zitron A.
    (1995) Drosophila eye development: Notch and Delta amplify a neurogenic pattern conferred on the morphogenetic furrow by scabrous. Mech. Dev 49, 173–189
    OpenUrlCrossRefPubMedWeb of Science
    1. Banerjee U.,
    2. Renfranz P. J.,
    3. Pollock J. A.,
    4. Benzer S.
    (1987) Molecular characterization and expression of sevenless, a gene involved in neuronal pattern formation in the Drosophila eye. Cell 49, 281–291
    OpenUrlCrossRefPubMedWeb of Science
    1. Bang A. G.,
    2. Hartenstein V.,
    3. Posakony J. W.
    (1991) Hairless is required for the development of adult sensory organ precursor cells in Drosophila. Development 111, 89–104
    OpenUrlAbstract
    1. Bang A. G.,
    2. Posakony J. W.
    (1992) The Drosophila gene Hairless encodes a novel basic protein that controls alternative cell fates in adult sensory organ development. Genes Dev 6, 1752–1769
    OpenUrlAbstract/FREE Full Text
    1. Basler K.,
    2. Siegrist P.,
    3. Hafen E.
    (1989) The spatial and temporal expression pattern of sevenless is exclusively controlled by gene-internal elements. EMBO J 8, 2381–2386
    OpenUrlPubMedWeb of Science
    1. Bowtell D. D. L.,
    2. Kimmel B. E.,
    3. Simon M. A.,
    4. Rubin G. M.
    (1989) Regulation of the complex pattern of sevenless expression in the developing Drosophila eye. Proc. Natl. Acad. Sci. USA 86, 6245–6249
    OpenUrlAbstract/FREE Full Text
    1. Bowtell D. D. L.,
    2. Lila T.,
    3. Michael W. M.,
    4. Hackett D.,
    5. Rubin G. M.
    (1991) Analysis of the enhancer element that controls expression of sevenless in the developing Drosophila eye. Proc. Natl. Acad. Sci. USA 88, 6853–6857
    OpenUrlAbstract/FREE Full Text
    1. Brou C.,
    2. Logeat F.,
    3. Lecourtois M.,
    4. Vandekerckhove J.,
    5. Kourilsky P.,
    6. Schweisguth F.,
    7. Israël A.
    (1994) Inhibition of the DNA-binding activity of DrosophilaSuppresser of Hairless and of its human homolog, KBF2/RBP-Jk, by direct protein-protein interaction with Drosophila Hairless. Genes Dev 8, 2491–2503
    OpenUrlAbstract/FREE Full Text
    1. Cagan R. L.,
    2. Ready D. F.
    (1989) Notch is required for successive cell decisions in the developing Drosophila retina. Genes Dev 3, 1099–1112
    OpenUrlAbstract/FREE Full Text
    1. Carthew R. W.,
    2. Rubin G. M.
    (1990) seven in absentia, a gene required for specification of R7 cell fate in the Drosophila eye. Cell 63, 561–577
    OpenUrlCrossRefPubMedWeb of Science
    1. Chitnis A.,
    2. Henrique D.,
    3. Lewis J.,
    4. Ish-Horowicz D.,
    5. Kintner C.
    (1995) Primary neurogenesis in Xenopus embryos regulated by a homolog of the Drosophila neurogenic gene Delta. Nature 375, 761–766
    OpenUrlCrossRefPubMedWeb of Science
    1. Coffman C. R.,
    2. Skoglund P.,
    3. Harris W. A.,
    4. Kintner C. R.
    (1993) Expression of an extracellular deletion of Xotch diverts cell fate in Xenopus embryos. Cell 73, 659–671
    OpenUrlCrossRefPubMedWeb of Science
    1. Fehon R. G.,
    2. Johansen K.,
    3. Rebay I.,
    4. Artavanis-Tsakonas S.
    (1991) Complex cellular and subcellular regulation of Notch expression during embryonic and imaginal development of Drosophila: implications for Notch function. J. Cell Biol 113, 657–669
    OpenUrlAbstract/FREE Full Text
    1. Fehon R. G.,
    2. Kooh P. J.,
    3. Rebay I.,
    4. Regan C. L.,
    5. Xu T.,
    6. Muskavitch M. A.,
    7. Artavanis-Tsakonas S.
    (1990) Molecular interactions between the protein products of the neurogenic loci Notch and Delta, two EGF-homologous genes in Drosophila. Cell 61, 523–534
    OpenUrlCrossRefPubMedWeb of Science
    1. Fitzgerald K.,
    2. Greenwald I.
    (1995) Interchangeability of Caenorhabditis elegans DSL proteins and intrinsic signalling activity of their extracellular domains in vivo. Development 121, 4275–4282
    OpenUrlAbstract
    1. Fleming R. J.,
    2. Scottgale T. M.,
    3. Diederich R. J.,
    4. Artavanis-Tsakonas S.
    (1990) The gene Serrate encodes a putative EGF-like transmembrane protein essential for proper ectodermal development in Drosophila melanogaster. Genes Dev 4, 2188–2201
    OpenUrlAbstract/FREE Full Text
    1. Fortini M. E.,
    2. Simon M. A.,
    3. Rubin G. M.
    (1992) Signalling by the sevenless protein tyrosine kinase is mimicked by Ras1 activation. Nature 336, 559–561
    OpenUrl
    1. Fortini M. E.,
    2. Rebay I.,
    3. Caron L. A.,
    4. Artavanis-Tsakonas S.
    (1993) An activated Notch receptor blocks cell-fate commitment in the developing Drosophila eye. Nature 365, 555–557
    OpenUrlCrossRefPubMedWeb of Science
    1. Gaul U.,
    2. Mardon G.,
    3. Rubin G. M.
    (1992) A putative Ras GTPase activating protein acts as a negative regulator of signalling by the sevenless receptor tyrosine kinase. Cell 68, 1007–1019
    OpenUrlCrossRefPubMedWeb of Science
    1. Gu Y.,
    2. Hukriede N. A.,
    3. Fleming R. J.
    (1995) Serrate expression can functionally replace Delta activity during neuroblast segregation in the Drosophila embryo. Development 121, 855–865
    OpenUrlAbstract
    1. Henderson S. T.,
    2. Gao D.,
    3. Lambie E. J.,
    4. Kimble J.
    (1994) lag-2 may encode a signaling ligand for the Glp-1 and Lin-12 receptors of C. elegans. Development 120, 2913–2924
    OpenUrlAbstract
    1. Henrique D.,
    2. Adam J.,
    3. Myat A.,
    4. Chitnis A.,
    5. Lewis J.,
    6. Ish-Horowicz D.
    (1995) Expression of a Delta homolog in prospective neurons in the chick. Nature 375, 787–790
    OpenUrlCrossRefPubMedWeb of Science
    1. Higashijima S.,
    2. Kojima T.,
    3. Michiue T.,
    4. Ishimaru S.,
    5. Emori Y.,
    6. Saigo K.
    (1992) Dual Bar homeo box genes of Drosophila required in two photoreceptor cells, R1 and R6, and primary pigment cells for normal eye development. Genes Dev 6, 50–60
    OpenUrlAbstract/FREE Full Text
    1. Jennings B.,
    2. Preiss A.,
    3. Delidakis C.,
    4. Bray S.
    (1994) The Notch signaling pathway is required for Enhancer of split bHLH protein expression during neurogenesis in the Drosophila embryo. Development 120, 3537–3548
    OpenUrlAbstract
    1. Jennings B.,
    2. de Celis J.,
    3. Delidakis C.,
    4. Preiss A.,
    5. Bray S.
    (1995) Role of Notch and achaete-scute complex in the expression of Enhancer of split bHLH proteins. Development 121, 3745–3752
    OpenUrlAbstract
    1. Kimmel B. E.,
    2. Heberlein U.,
    3. Rubin G. M.
    (1990) The homeo domain protein rough is expressed in a subset of cells in the developing Drosophila eye where it can specify photoreceptor cell subtype. Genes Dev 4, 712–727
    OpenUrlAbstract/FREE Full Text
    1. Kooh P. J.,
    2. Fehon R. G.,
    3. Muskavitch M. A. T.
    (1993) Implications of dynamic patterns of Delta and Notch expression for cellular interactions during Drosophila development. Development 117, 493–507
    OpenUrlAbstract
    1. Kopczynski C. C.,
    2. Alton A. K.,
    3. Fechtel K.,
    4. Kooh P. H.,
    5. Muskavitch M. A.
    (1988) Delta, a Drosophila neurogenic gene, is transcriptionallycomplex and encodes a protein related to blood coagulation factors and epidermal growth factors of vertebrates. Genes Dev 2, 1723–1735
    OpenUrlAbstract/FREE Full Text
    1. Kreis T. E.
    (1986) Microinjected antibodies against the cytoplasmic domain of vesicular stomatitis virus glycoprotein block its transport to the cell surface. EMBO J 5, 931–941
    OpenUrlPubMedWeb of Science
    1. Lindsell C. E.,
    2. Shawber C. J.,
    3. Boulter J.,
    4. Weinmaster G.
    (1995) Jagged: a mammalian ligand that activates Notch1. Cell 80, 909–917
    OpenUrlCrossRefPubMedWeb of Science
    1. Matsuno K.,
    2. Diederich R. J.,
    3. Go M. J.,
    4. Blaumueller C. M.,
    5. Artavanis-Tsakonas
    (1995) Deltex acts as a positive regulator of Notch signalling through interactions with the Notch ankyrin repeats. Development 121, 2633–2644
    OpenUrlAbstract
    1. Mello C. C.,
    2. Draper B. W.,
    3. Priess J. R.
    (1994) The maternal genes apx-1 and glp-1 and establishment of dorsal-ventral polarity in the early C. elegans embryo. Cell 77, 95–106
    OpenUrlCrossRefPubMedWeb of Science
    1. Moffat K. G.,
    2. Gould J. H.,
    3. Smith H. K.,
    4. O'Kane C. J.
    (1992) Inducible cell ablation in Drosophila by cold-sensitive ricin A chain. Development 114, 681–687
    OpenUrlAbstract
    1. Muskavitch M. A. T.
    (1994) Delta-Notch signaling and Drosophila cell fate choice. Dev. Biol 166, 415–430
    OpenUrlCrossRefPubMedWeb of Science
    1. O'Toole T. E.,
    2. Katagiri Y.,
    3. Faull R. J.,
    4. Peter K.,
    5. Tamura R.,
    6. Quaranta V.,
    7. Loftus J. D.,
    8. Shattil S. J.,
    9. Ginsburg M. H.
    (1994) Integrin cytoplasmic domains mediate inside-out signal transduction. J. Cell Biol 124, 1047–1059
    OpenUrlAbstract/FREE Full Text
    1. Parks A. L.,
    2. Turner F. R.,
    3. Muskavitch M. A. T.
    (1995) Relationships between complex Delta expression and the specification of retinal cell fates during Drosophila eye development. Mech. Dev 50, 201–216
    OpenUrlCrossRefPubMedWeb of Science
    1. Rabinow L.,
    2. Birchler J. A.
    (1990) Interactions of vestigial and scabrous with the Notch locus of Drosophila melanogaste r. Genetics 125, 41–50
    OpenUrlAbstract/FREE Full Text
    1. Rebay I.,
    2. Fehon R. G.,
    3. Artavanis-Tsakonas S.
    (1993) Specific truncations of Drosophila Notch define dominant activated and dominant negative forms of the receptor. Cell 74, 319–329
    OpenUrlCrossRefPubMedWeb of Science
    1. Rebay I.,
    2. Fleming R. J.,
    3. Fehon R. G.,
    4. Cherbas L.,
    5. Cherbas P.,
    6. Artavanis-Tsakonas S.
    (1991) Specific EGF repeats of Notch mediate interactions with Delta and Serrate: implications for Notch as a multifunctional receptor. Cell 67, 687–699
    OpenUrlCrossRefPubMedWeb of Science
    1. Struhl G.,
    2. Fitzgerald K.,
    3. Greenwald I.
    (1993) Intrinsic activity of the Lin-12 and Notch intracellular domains in vivo. Cell 74, 331–345
    OpenUrlCrossRefPubMedWeb of Science
    1. Tata F.,
    2. Hartley D. A.
    (1995) Inhibition of cell fate in Drosophila by Enhancer of split genes. Mech. Dev 51, 305–315
    OpenUrlCrossRefPubMed
    1. Tax F. E.,
    2. Yeargers J. J.,
    3. Thomas J. H.
    (1994) Sequence of C. elegans lag-2 reveals a cell-signalling domain shared with Delta and Serrate of Drosophila. Nature 368, 150–154
    OpenUrlCrossRefPubMed
    1. Thomas U.,
    2. Speicher S. A.,
    3. Knust E.
    (1991) The Drosophila gene Serrate encodes an EGF-like transmembrane protein with a complex expression pattern in embryos and wing discs. Development 111, 749–761
    OpenUrlAbstract
    1. Tomlinson A.,
    2. Bowtell D. D. L.,
    3. Hafen E.,
    4. Rubin G. M.
    (1987) Localization of the sevenless protein, a putative receptor for positional information, in the eye imaginal disc of Drosophila. Cell 51, 143–150
    OpenUrlCrossRefPubMedWeb of Science
    1. Vässin H.,
    2. Bremer K. A.,
    3. Knust E.,
    4. Campos-Ortega J. A.
    (1987) The neurogenic gene Delta of Drosophila melanogaster is expressed in neurogenic territories and encodes a putative transmembrane protein with EGF-like repeats. EMBO J 6, 3433–3440
    OpenUrl
    1. Wharton K. A.,
    2. Johansen K. M.,
    3. Xu T.,
    4. Artavanis-Tsakonas S.
    (1985) Nucleotide sequence from the neurogenic locus Notch implies a gene product that shares homology with proteins containing EGF-like repeats. Cell 43, 567–581
    OpenUrlCrossRefPubMedWeb of Science
    1. Wilkinson H.,
    2. Fizgerald K.,
    3. Greenwald I.
    (1994) Reciprocal changes in expression of the receptor lin-12 and its ligand lag-2 prior to commitment in a C. elegans cell fate decision. Cell 79, 1187–1198
    OpenUrlCrossRefPubMedWeb of Science
    1. Xu T.,
    2. Rubin G. M.
    (1993) Analysis of genetic mosaics in developing and adult Drosophila tissues. Development 117, 1223–1237
    OpenUrlAbstract
    1. Zabin I.
    (1982) -Galactosidase -complementation: a model of protein-protein interaction. Mol. Cell. Biochem 49, 87–96
    OpenUrlPubMedWeb of Science
    1. Zervos A. S.,
    2. Gyuris J.,
    3. Brent R.
    (1993) Mxi1, a protein that specifically interacts with Max to bind Myc-Max recognition sites. Cell 72, 223–232
    OpenUrlCrossRefPubMedWeb of Science
    1. Zipursky S. L.,
    2. Rubin G. M.
    (1994) Determination of neuronal cell fate: lessons from the R7 neuron of Drosophila. Annu. Rev. Neurosci 17, 373–397
    OpenUrlCrossRefPubMedWeb of Science
Back to top

 Download PDF

Email
JOURNAL ARTICLES
The intracellular deletions of Delta and Serrate define dominant negative forms of the Drosophila Notch ligands
X. Sun, S. Artavanis-Tsakonas
Development 1996 122: 2465-2474;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Alerts

Article navigation

Other journals from The Company of Biologists

Advertisement

An interview with Swathi Arur

Swathi Arur joined the team at Development as an Academic Editor in 2020. Her lab uses multidisciplinary approaches to understand female germline development and fertility. We met with her over Zoom to hear more about her life, her career and her love for C. elegans.

Jim Wells and Hanna Mikkola join our team of Editors

We are pleased to welcome James (Jim) Wells and Hanna Mikkola to our team of Editors. Jim joins us a new Academic Editor, taking over from Gordan Keller, and Hanna joins our team of Associate Editors. Find out more about their research interests and areas of expertise.

New funding scheme supports sustainable events

As part of our Sustainable Conferencing Initiative, we are pleased to announce funding for organisers that seek to reduce the environmental footprint of their event. The next deadline to apply for a Scientific Meeting grant is 26 March 2021.

Read & Publish participation continues to grow

“I’d heard of Read & Publish deals and knew that many universities, including mine, had signed up to them but I had not previously understood the benefits that these deals bring to authors who work at those universities.”

Professor Sally Lowell (University of Edinburgh) shares her experience of publishing Open Access as part of our growing Read & Publish initiative. We now have over 150 institutions in 15 countries and four library consortia taking part – find out more and view our full list of participating institutions.

Upcoming special issues

Imaging Development, Stem Cells and Regeneration
Submission deadline: 30 March 2021
Publication: mid-2021

The Immune System in Development and Regeneration
Guest editors: Florent Ginhoux and Paul Martin
Submission deadline: 1 September 2021
Publication: Spring 2022

Both special issues welcome Review articles as well as Research articles, and will be widely promoted online and at key global conferences.

Development presents...

Our successful webinar series continues into 2021, with early-career researchers presenting their papers and a chance to virtually network with the developmental biology community afterwards. Here, Michèle Romanos talks about her new preprint, which mixes experimentation in quail embryos and computational modelling to understand how heterogeneity in a tissue influences cell rate.

Save your spot at our next session:

10 March
Time: 9:00 (GMT)
Chaired by: Thomas Lecuit

Join our mailing list to receive news and updates on the series.