Advertisement
JOURNAL ARTICLES
Cell proliferation control by Notch signaling in Drosophila development
M.J. Go, D.S. Eastman, S. Artavanis-Tsakonas
Development 1998 125: 2031-2040;

Summary

The Notch receptor mediates cell interactions controlling the developmental fate of a broad spectrum of undifferentiated cells. By modulating Notch signaling in specific precursor cells during Drosophila imaginal disc development, we demonstrate that Notch activity can influence cell proliferation. The activation of the Notch receptor in the wing disc induces the expression of the wing margin patterning genes vestigial and wingless, and strong mitotic activity. However, the effect of Notch signaling on cell proliferation is not the simple consequence of the upregulation of either vestigial or wingless. Vestigial and Wingless, on the contrary, display synergistic effects with Notch signaling, resulting in the stimulation of cell proliferation in imaginal discs.

REFERENCES

    1. Artavanis-Tsakonas S.,
    2. Matsuno K.,
    3. Fortini M. E.
    (1995) Notch signaling. Science 268, 225–232
    OpenUrlAbstract/FREE Full Text
    1. Bailey A. M.,
    2. Posakony J. W.
    (1995) Suppressor of Hairless directly activates transcription of Enhancer of split Complex genes in response to Notch receptor activity. Genes Dev 9, 2609–2622
    OpenUrlAbstract/FREE Full Text
    1. Bang A. G.,
    2. Bailey A. M.,
    3. Posakony J. W.
    (1995) Hairless promotes stable commitment to the sensory organ precursor cell fate by nagatively regulating the activity of the Notch signaling pathway. Dev. Biol 172, 479–494
    OpenUrlCrossRefPubMedWeb of Science
    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. Blackman R. K.,
    2. Sanicola M.,
    3. Raftery L. A.,
    4. Gillevet T.,
    5. Gelbart W. M.
    (1991) An extensive 3cis-regulatory region directs the imaginal disk expression of decapentaplegic, a member of the TGF-family in Drosophila. Development 111, 657–665
    OpenUrlAbstract
    1. Brand A.,
    2. Perrimon N.
    (1993) Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 401–415
    OpenUrlAbstract
    1. Brook W. J.,
    2. Diaz-Benjumea F. J.,
    3. Cohen S. M.
    (1996) Organizing spatial pattern in limb development. Annu. Rev. Cell Dev. Biol 12, 161–180
    OpenUrlCrossRefPubMedWeb of Science
    1. Brou C.,
    2. Logeat F.,
    3. Lecourtois M.,
    4. Vandekerckhove J.,
    5. Kourilsky P.,
    6. Schweisguth F.,
    7. Israel A.
    (1994) Inhibition of the DNA-binding activity of Drosophila Suppressor of Hairless and of its human homolog, KBF2/RBP-J, by direct protein-protein interaction with Drosophila Hairless. Genes Dev 8, 2491–2503
    OpenUrlAbstract/FREE Full Text
    1. Capobianco A. J.,
    2. Zagouras P.,
    3. Blaumueller C. M.,
    4. Artavanis-Tsakonas S.,
    5. Bishop J. M.
    (1997) Neoplastic transformation by truncated alleles of human NOTCH/TAN 1 and NOTCH 2. Mol. Cell Biol 17, 6265–6273
    OpenUrlAbstract/FREE Full Text
    1. Cohen S. M.
    (1996) Controlling growth of the wing: Vestigial integrates signals from the compartment boundaries. BioEssays 18, 855–858
    OpenUrlCrossRefPubMedWeb of Science
    1. Couso J. P.,
    2. Bate M.,
    3. Martinez-Arias A.
    (1993) A wingless -dependent polar coordinate system in the imaginal discs of Drosophila. Science 259, 484–489
    OpenUrlAbstract/FREE Full Text
    1. Couso J. P.,
    2. Knust E.,
    3. Martinez-Arias A.
    (1995) Serrate and wingless cooperate to induce vestigial gene expression and wing formation in Drosophila. Current Biol 5, 1437–1448
    OpenUrlCrossRefPubMedWeb of Science
    1. de Celis J. F.,
    2. Garcia-Bellido A.,
    3. Bray S. J.
    (1996) Activation and function of Notch at the dorsal-ventral boundary of the wing imaginal disc. Development 122, 359–369
    OpenUrlAbstract
    1. de Celis J. F.,
    2. Bray S.
    (1997) Feed-back mechanism affecting Notch activation at the dorsoventral boundary in the Drosophila wing. Development 124, 3241–3251
    OpenUrlAbstract
    1. de Nooji J. C.,
    2. Hariharan I. K.
    (1995) Uncoupling cell fate determination from patterned cell division in the Drosophila eye. Science 270, 983–985
    OpenUrlAbstract/FREE Full Text
    1. Diaz-Benjumea F. J.,
    2. Cohen S. M.
    (1995) Serrate signals through Notch to establish a Wingless-dependent organizer at the dorsal/ventral compartment boundary of the Drosophila wing. Development 121, 4215–4225
    OpenUrlAbstract
    1. Diederich R. J.,
    2. Matsuno K.,
    3. Hing H.,
    4. Artavanis-Tsakonas S.
    (1994) Cytosolic interaction between deltex and Notch ankyrin repeats implicates deltex in the Notch signaling pathway. Development 120, 473–481
    OpenUrlAbstract
    1. Doherty D.,
    2. Feger G.,
    3. Younger-Shepherd S.,
    4. Jan L. Y.,
    5. Jan Y. N.
    (1996) Delta is a ventral to dorsal signal complementary to Serrate, another Notch ligand in Drosophila wing formation. Genes Dev 10, 421–434
    OpenUrlAbstract/FREE Full Text
    1. Eastman D. S.,
    2. Slee R.,
    3. Skoufos E.,
    4. Bangalore L.,
    5. Bray S.,
    6. Delidakis C.
    (1997) Synergy between Suppressor of Hairless and Notch in regulation of Enhancer of split m and m expression. Mol. Cell Biol 17, 5620–5628
    OpenUrlAbstract/FREE Full Text
    1. Ellisen L. W.,
    2. Bird J.,
    3. West D. C.,
    4. Soreng A. L.,
    5. Reynolds T. C.,
    6. Smith S. D.,
    7. Sklar J.
    (1991) TAN-1, the human homolog of the Drosophila Notch gene, is broken by chromosomal translacations in T lymphoblastic neoplasms. Cell 66, 649–661
    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. Fortini M. E.,
    2. Artavanis-Tsakonas S.
    (1994) The Suppressor of Hairless protein paricipates in Notch receptor signaling. Cell 79, 273–282
    OpenUrlCrossRefPubMedWeb of Science
    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. Foster G. G.
    (1975) Negative complementation at the Notch locus of Drosophila melanogaster. Genetics 81, 99–120
    OpenUrlAbstract/FREE Full Text
    1. Gallahan D.,
    2. Gallahan R.
    (1997) The mouse mammary tumor associated gene INT3 is a unique member of the NOTCH gene family (NOTCH4). Oncogene 14, 1883–1890
    OpenUrlCrossRefPubMedWeb of Science
    1. Hartley D. A.,
    2. Xu T.,
    3. Artavanis-Tsakonas S.
    (1987) The embryonic expression of the Notch locus of Drosophilamelanogaster and the implications of point mutations in the extracellular EGF-like domain of the predicted protein. EMBO J 6, 3407–3417
    OpenUrlPubMedWeb of Science
    1. Heitzler P.,
    2. Simpson P.
    (1993) Altered epidermal growth factor-like sequences provide evidence for a role of Notch as a receptor in cell fate decisions. Development 117, 1113–1123
    OpenUrlAbstract
    1. Hukriede N. A.,
    2. Fleming R. J.
    (1997) Beaded of Goldschmidt, an antimorphic allele of Serrate, encodes a protein lacking transmembrane and intracellular domains. Genetics 145, 359–374
    OpenUrlAbstract/FREE Full Text
    1. Irvine K. D.,
    2. Vogt T. F.
    (1997) Dorsal-ventral signaling in limb development. Curr. Opinion in Cell Biol 9, 867–876
    OpenUrlCrossRefPubMedWeb of Science
    1. Jarriault S.,
    2. Brou C.,
    3. Logeat F.,
    4. Schroeter E. H.,
    5. Kopan R.,
    6. Israel A.
    (1995) Signalling downstream of activated mammalian Notch. Nature 377, 355–358
    OpenUrlCrossRefPubMedWeb of Science
    1. Jhappan C.,
    2. Gallahan D.,
    3. Stahle C.,
    4. Chu E.,
    5. Smith G. H.,
    6. Marlino G.,
    7. Callahan R.
    (1992) Expression of an activated Notch -related int-3 transgene interferes with cell defferentiation and induces neoplastic transformation in mammary and salivary glands. Genes Dev 6, 345–355
    OpenUrlAbstract/FREE Full Text
    1. Kassis J. A.,
    2. Noll E.,
    3. VanSickle E. P.,
    4. Odenwald W. F.,
    5. Perrimon N.
    (1992) Altering insertional specificity of a Drosophila transposable element. Proc. Natl. Acad. Sci. USA 89, 1919–1923
    OpenUrlAbstract/FREE Full Text
    1. Kelly M. R.,
    2. Kidd S.,
    3. Deutsch W. A.,
    4. Young M. W.
    (1987) Mutations altering the structure of epidermal growth factor-like coding sequences at the DrosophilaNotch locus. Cell 51, 539–548
    OpenUrlCrossRefPubMedWeb of Science
    1. Kim J.,
    2. Irvine K. D.,
    3. Carroll S. B.
    (1995) Cell recognition, signal induction and symmetrical gene activation at the dorsal/ventral boundary of the developing Drosophila wing. Cell 82, 795–802
    OpenUrlCrossRefPubMedWeb of Science
    1. Kim J.,
    2. Sebring A.,
    3. Esch J. J.,
    4. Kraus M. E.,
    5. Vorwerk K.,
    6. Magee J.,
    7. Carroll S. B.
    (1996) Integration of positional signals and regulation of wing formation and identity by Drosophila vestigial gene. Nature 382, 133–138
    OpenUrlCrossRefPubMed
    1. Lawrence P. A.,
    2. Bodmer R.,
    3. Vincent J. P.
    (1995) Segmental patterning of heart mesoderm in Drosophila. Development 121, 4303–4308
    OpenUrlAbstract
    1. Lecourtois M.,
    2. Schweisguth F.
    (1995) 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 9, 2598–2608
    OpenUrlAbstract/FREE Full Text
    1. Lieber T.,
    2. Kidd S.,
    3. Alcamo E.,
    4. Corbin V.,
    5. Young M. W.
    (1993) Antineurogenic phenotypes induced by truncated Notch proteins indicate a role in signal transduction and may point to a novel function for Notch in nuclei. Genes Dev 7, 1949–1965
    OpenUrlAbstract/FREE Full Text
    1. Lyman D. F.,
    2. Yedvodnick B.
    (1995) Drosophila Notch receptor activity suppresses Hairless function during adult external sensory organ development. Genetics 141, 1491–1505
    OpenUrlAbstract/FREE Full Text
    1. Maier D.,
    2. Stumm G.,
    3. Kuhn K.,
    4. Preiss A.
    (1992) Hairless, a Drosophila gene involved in neural development, encodes a novel, serine rich protein. Mech. Dev 38, 143–156
    OpenUrlCrossRefPubMedWeb of Science
    1. Markopoulou K.,
    2. Artavanis-Tsakonas S.
    (1989) The expression of the neurogenic locus Notch during the postembryonic development of Drosophila melanogaster and its relationship to mitotic activity. J. Neurogenet 6, 11–26
    OpenUrlCrossRefPubMed
    1. Matsuno K.,
    2. Go M. J.,
    3. Sun X.,
    4. Eastman D. S.,
    5. Artavanis-Tsakonas S.
    (1997) Suppressor of Hairless-independent events in Notch signaling imply novel pathway elements. Development 124, 4265–4273
    OpenUrlAbstract
    1. Moon R. T.,
    2. Miller J. R.
    (1997) The APC tumor suppressor protein in development and cancer. Trends Genet 13, 256–258
    OpenUrlCrossRefPubMedWeb of Science
    1. Neumann C. J.,
    2. Cohen S. M.
    (1996) Distinct mitogenic and cell fate specification functions of wingless in different regions of the wing. Development 122, 1781–1789
    OpenUrlAbstract
    1. Neumann C. J.,
    2. Cohen S. M.
    (1996) A hierarchy of cross-regulation involving Notch, wingless, vestigial and cut organizes the dorsal/ventral axis of the Drosophila wing. Development 122, 3477–3485
    OpenUrlAbstract
    1. Neumann C. J.,
    2. Cohen S. M.
    (1997) Long-range action of Wingless organizes the dorsal-ventral axis of the Drosophila wing. Development 124, 871–880
    OpenUrlAbstract
    1. Ng M.,
    2. Diaz-Benjumea F. J.,
    3. Vincent J.-P.,
    4. Wu J.,
    5. Cohen S. M.
    (1996) Specification of the wing by localized expression of wingless protein. Nature 381, 316–318
    OpenUrlCrossRefPubMed
    1. Nusse R.,
    2. Varmus H. E.
    (1992) Wnt genes. Cell 69, 1073–1087
    OpenUrlCrossRefPubMedWeb of Science
    1. O'Brochta D.,
    2. Bryant P. J.
    (1985) A zone of non-proliferating cells at a lineage restriction boundary in Drosophila. Nature 313, 138–141
    OpenUrlCrossRefPubMed
    1. Phillips R. G.,
    2. Whittle J. R. S.
    (1993) wingless expression mediatesdetermination of peripheral nervous system elements in late stages of Drosophila wing disc development. Development 118, 427–438
    OpenUrlAbstract
    1. Portin P.
    (1975) Allelic negative complementation at the Abruptex locus of Drosophila melanogaster. Genetics 81, 121–133
    OpenUrlAbstract/FREE Full Text
    1. Rebay I.,
    2. Fehon R. G.,
    3. Artavanis-Tsakonas S.
    (1993) Specific truncation of Drosophila Notch define dominant activated and dominant negative forms of the receptor. Cell 74, 319–329
    OpenUrlCrossRefPubMedWeb of Science
    1. Robbins J.,
    2. Blondel B. J.,
    3. Gallahan D.,
    4. Gallahan R.
    (1992) Mouse mammary tumor gene int-3: a member of the Notch gene family transforms mammary epithelial cells. J. Virol 66, 2594–2599
    OpenUrlAbstract/FREE Full Text
    1. Rulifson E. J.,
    2. Blair S. S.
    (1995) Notch regulates wingless expression and is not required for reception of the paracrine wingless signal during wing margin neurogenesis in Drosophila. Development 121, 2813–1824
    OpenUrlAbstract
    1. Rulifson E. J.,
    2. Micchelli C. A.,
    3. Axelrod J. D.,
    4. Perrimon N.,
    5. Blair S. S.
    (1996) wingless refines its own expression domain on the Drosophila wing margin. Nature 384, 72–74
    OpenUrlCrossRefPubMed
    1. Schubiger M.,
    2. Palka J.
    (1987) Changing spatial patterns of DNA replication in the developing wing of Drosophila. Dev. Biol 123, 145–153
    OpenUrlCrossRefPubMedWeb of Science
    1. Schweisguth F.,
    2. Posakony J. W.
    (1994) Antagonistic activities of Suppressor of Hairless and Hairless control alternative cell fates in the Drosophila adult epidermis. Development 120, 1433–1441
    OpenUrlAbstract
    1. Shawber C.,
    2. Nofziger D.,
    3. Hsieh J. J.-D.,
    4. Lindsell C.,
    5. Bogler O.,
    6. Hayward D.,
    7. Weinmaster G.
    (1996) Notch signaling inhibits muscle cell differentiation through a CBF1-independent pathway. Development 122, 3765–3773
    OpenUrlAbstract
    1. Speicher S. A.,
    2. Thomas U.,
    3. Hinz U.,
    4. Knust E.
    (1994) The Serrate locus of Drosophila and its role in morphogenesis of the wing imaginal discs: control of cell proliferation. Development 120, 535–544
    OpenUrlAbstract
    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. Sun X.,
    2. Artavanis-Tsakonas S.
    (1997) Secreted forms of DELTA and SERRATE define antagonists of Notch signaling in Drosophila. Development 124, 3439–3448
    OpenUrlAbstract
    1. Tamura K.,
    2. Taniguchi Y.,
    3. Minoguchi S.,
    4. Sakai T.,
    5. Tun T.,
    6. Furukawa T.,
    7. Honjo T.
    (1995) Physical interaction between a novel domain of the receptor Notch and the transcription factor RBP-J/Su(H). Current Biol 5, 1416–1423
    OpenUrlCrossRefPubMedWeb of Science
    1. Uyttendaele H.,
    2. Marazzi G.,
    3. Wu G.,
    4. Yan Q.,
    5. Sassoon D.,
    6. Kitajewski J.
    (1996) Notch4/int-3, a mammary proto-oncogene, is an endothelial cell-specific mammalian Notch gene. Development 12, 2251–2259
    OpenUrl
    1. Wang S.,
    2. Younger-Shepherd S.,
    3. Jan L. Y.,
    4. Jan Y. N.
    (1997) Only a subset of the binary cell fate decisions mediated by Numb/Notch signaling in Drosophila sensory organ lineage requires Suppressor of Hairless. Development 124, 4435–4446
    OpenUrlAbstract
    1. Williams J. A.,
    2. Paddock S. W.,
    3. Carroll S. B.
    (1993) Pattern formation in a secondary field: a hierarchy of regulatory genes subdivides the developing Drosophila wing disc into discrete subregions. Development 117, 571–584
    OpenUrlAbstract
    1. Williams J. A.,
    2. Paddock S. W.,
    3. Vorwerk K.,
    4. Carroll S. B.
    (1994) Organization of wing formation and induction of a wing-patterning gene at the dorsal/ventral compartment boundary. Nature 368, 299–305
    OpenUrlCrossRefPubMed
    1. Zecca M.,
    2. Basler K.,
    3. Struhl G.
    (1996) Direct and long-range action of a wingless morphogen gradient. Cell 87, 833–844
    OpenUrlCrossRefPubMedWeb of Science
Back to top

 Download PDF

Email
JOURNAL ARTICLES
Cell proliferation control by Notch signaling in Drosophila development
M.J. Go, D.S. Eastman, S. Artavanis-Tsakonas
Development 1998 125: 2031-2040;
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

Kathryn Virginia Anderson (1952-2020)

Developmental geneticist Kathryn Anderson passed away at home on 30 November 2020. Tamara Caspary, a former postdoc and friend, remembers Kathryn and her remarkable contribution to developmental biology.

Zooming into 2021

In a new Editorial, Editor-in-Chief James Briscoe and Executive Editor Katherine Brown reflect on the triumphs and tribulations of the last 12 months, and look towards a hopefully calmer and more predictable year.

Read & Publish participation extends worldwide

Over 60 institutions in 12 countries are now participating in our Read & Publish initiative. Here, James Briscoe explains what this means for his institution, The Francis Crick Institute. 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. Sign up to join our next session:

10 February
Time: 13:00 (GMT)
Chaired by: preLights