Advertisement
JOURNAL ARTICLES
The intracellular domain of mouse Notch: a constitutively activated repressor of myogenesis directed at the basic helix-loop-helix region of MyoD
R. Kopan, J.S. Nye, H. Weintraub
Development 1994 120: 2385-2396;

Summary

We show that Myf-5 and mNotch mRNA are both present in the presomitic mesoderm before muscle cell commitment and before muscle structural gene activation. The failure of presomitic mesoderm to respond to Myf-5 and express myogenic properties implies that there may be a mechanism in presomitic mesoderm to suppress muscle differentiation. Here we show that ectopic expression of the intracellular domain of mNotch (mNotchIC) functions as a constitutively activated repressor of myogenesis both in cultured cells and in frog embryos. Mutagenesis experiments indicate that the target for inactivation by mNotch is the MyoD basic helix-loop-helix domain. mNotchIC contains a nuclear localization signal and localizes to the nucleus. Removal of the nuclear localization signal (NLS) reduces nuclear localization and diminishes the inhibition of myogenesis caused by Myf-5 or MyoD. Additional experiments show that the CDC10/SWI6/ankyrin repeats are also necessary for myogenic inhibition.

REFERENCES

    1. Alonso M. C.,
    2. Cabrera C. V.
    (1988) The achaete-scute gene complex of Drosophila melanogaster comprises four homologous genes. EMBO J 7, 3899–3906
    OpenUrlPubMedWeb of Science
    1. Artavanis-Tsakonas S.,
    2. Simpson P.
    (1991) Choosing a cell fate: a view from the Notch locus. Trends Genetics 7, 403–408
    OpenUrlCrossRefPubMedWeb of Science
    1. Bader D.,
    2. Masaki T.,
    3. Fischmann D. A.
    (1982) Immunological analysis of myosin heavy chain during avian myogenesis in vitro and in vivo. J. Biol. Chem 95, 763–770
    OpenUrl
    1. Breeden L.,
    2. Nasmyth K.
    (1987) Similarity between cell-cycle genes of budding yeast and fission yeast and the Notch gene of Drosophila. Nature 329, 651–654
    OpenUrlCrossRefPubMed
    1. Buonanno A.,
    2. Apone L.,
    3. Morasso M. I.,
    4. Beers R.,
    5. Brenner H. R.,
    6. Eftimie R.
    (1992) The MyoD family of myogenic factors is regulated by electrical activity: isolation and characterization of the mouse Myf-5 cDNA. Nucleic Acids Res 20, 539–544
    OpenUrlAbstract/FREE Full Text
    1. Cabrera C. V.
    (1990) Lateral inhibition and cell fate during neurogenesis in Drosophila: the interactions between scute, notch and delta. Development 109, 733–742
    OpenUrlAbstract
    1. Cabrera C. V.
    (1992) The generation of cell diversity during early neurogenesis in Drosophila. Development 115, 893–901
    OpenUrlPubMedWeb of Science
    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. Campos-Ortega J. A.
    (1993) Mechanisms of early neurogenesis in Drosophila melanogaster. [Review]. J. Neurobiology 24, 1305–27
    OpenUrlCrossRefPubMedWeb of Science
    1. Campuzano S.,
    2. Modolell J.
    (1992) Patterning of the Drosophila nervous system: the achaete-scute gene complex. [Review]. Trends in Genetics 8, 202–208
    OpenUrlCrossRefPubMedWeb of Science
    1. Chomczynski P.,
    2. Sacchi N.
    (1987) Single step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Analyt. Biochem 162, 156–159
    OpenUrlCrossRefPubMedWeb of Science
    1. Coffman C.,
    2. Skoglund P.,
    3. Harris W. A.,
    4. Kintner C. R.
    (1993) Expression of an extracellular domain of Xotch diverts cell fates in Xenopus embryos. Cell 73, 659–671
    OpenUrlCrossRefPubMedWeb of Science
    1. Coffman C.,
    2. Harris W.,
    3. Kintner C.
    (1990) Xotch, the Xenopus homolog of Drosophila Notch. Science 249, 1438–1441
    OpenUrlAbstract/FREE Full Text
    1. Corbin V.,
    2. Michelson A. M.,
    3. Abmayr S. M.,
    4. Neel V.,
    5. Alcamo E.,
    6. Maniatis T.,
    7. Young M. W.
    (1991) A role for the Drosophila neurogenic genes in mesoderm differentiation. Cell 67, 311–323
    OpenUrlCrossRefPubMedWeb of Science
    1. Davis R. L.,
    2. Weintraub H.
    (1992) Acquisition of myogenic specificity by replacement of three amino acid residues from MyoD into E12. Science 256, 1027–30
    OpenUrlAbstract/FREE Full Text
    1. De Celis J. F.,
    2. Barrio R.,
    3. del Arco A.,
    4. Garcia-Bellido A.
    (1993) Genetic and molecular characterization of a Notch mutation in its Delta-and Serrate-binding domain in Drosophila. Proc. Natl. Acad. Sci. USA 90, 4037–4041
    OpenUrlAbstract/FREE Full Text
    1. De Celis J. F.,
    2. Mari-Beffa M.,
    3. Garcia-Bellido A.
    (1991) Cell-autonomous role of Notch, an epidermal growth factor homologue, in sensory organ differentiation in Drosophila. Proc. Natl. Acad. Sci. USA 88, 632–636
    OpenUrlAbstract/FREE Full Text
    1. Ellisen L. W.,
    2. Bird J.,
    3. West D. C.,
    4. Soreng T. C.,
    5. Reynolds A. L.,
    6. Smith S. D.,
    7. Sklar J.
    (1991) TAN-1, the human homolog of the Drosophila Notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell 66, 649–661
    OpenUrlCrossRefPubMedWeb of Science
    1. Evan G. I.,
    2. Lewis G. K.,
    3. Ramsay G.,
    4. Bishop M.
    (1985) Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product. Mol. Cell. Biol 5, 3610–3616
    OpenUrlAbstract/FREE Full Text
    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. Fortini M. E.,
    2. Rebay I.,
    3. Caron L. A.,
    4. Artavanis ,
    5. Tsakonas S.
    (1993) An activated Notch receptor blocks cell-fate commitment in the developing Drosophila eye. Nature 365, 555–557
    OpenUrlCrossRefPubMedWeb of Science
    1. Franco Del Amo F.,
    2. Smith D. E.,
    3. Swiatek P. J.,
    4. Gendron-Meguire M.,
    5. Greenspan R. J.,
    6. McMahon A. P.,
    7. Gridley T.
    (1992) Expression pattern of Motch, a mouse homolog of DrosophilaNotch, suggests an important role in early postimplantation mouse development. Development 115, 737–744
    OpenUrlAbstract/FREE Full Text
    1. Gearhart J. D.,
    2. Mintz B.
    (1972) Clonal origins of somites and their muscle derivatives: evidence from allophenic mice. Dev. Biol 29, 27–37
    OpenUrlCrossRefPubMedWeb of Science
    1. Ghysen A.,
    2. Dambly-Chaudiere C.,
    3. Jan L. Y.,
    4. Jan Y. N.
    (1993) Cell interactions and gene interactions in peripheral neurogenesis. Genes Dev 7, 723–733
    OpenUrlFREE Full Text
    1. Godsave S. F.,
    2. Slack J. M. W.
    (1989) Clonal analysis of mesoderm induction in Xenopus laevis. Dev. Biol 134, 486–490
    OpenUrlCrossRefPubMedWeb of Science
    1. Goriely A.,
    2. Dunont N.,
    3. Dambly-Chaudiere C.,
    4. Ghysen A.
    (1991) The determination of sense organs in Drosophila: effects of the neurogenic mutation in the embryo. Development 113, 1395–1404
    OpenUrlAbstract
    1. Goulding M.,
    2. Lumsden A.,
    3. Paquette A. J.
    (1994) Regulation of Pax-3 expression in the dermomyotome and its role in muscle development. Development 120, 957–971
    OpenUrlAbstract
    1. Greenwald I.,
    2. Rubin G.
    (1992) Making a difference: the role of cell-cell interactions in establishing separate identities for equivalent cells. Cell 68, 271–281
    OpenUrlCrossRefPubMedWeb of Science
    1. Heitzler P.,
    2. Simpson P.
    (1991) The choice of cell fate in the epidermis of Drosophila. Cell 64, 1083–1092
    OpenUrlCrossRefPubMedWeb of Science
    1. Heitzler P.,
    2. Simpson P.
    (1993) Altered epidermal growth factor likesequences provide evidence for a role of Notch as a receptor in cell fate decisions. Development 117, 1113–1123
    OpenUrlAbstract
    1. Hemmati-Brivanlou A.,
    2. Harland M. R.
    (1989) Expression of an engrailed-related protein is induced in the anterior neural ectoderem of early Xenopus embryos. Development 106, 611–617
    OpenUrlAbstract
    1. Hinz U.,
    2. Giebel B.,
    3. Campos-Ortega J. A.
    (1994) The basic helix-loop-helix domain of Drosophila lethal of scute protein is sufficient for proneural function and activates neurogenic genes. Cell 76, 77–87
    OpenUrlCrossRefPubMedWeb of Science
    1. Holtzer H.,
    2. Detwiler S. R.
    (1953) An experimental analysis of the development of the spinal column. J. Exp. Zool 123, 335–369
    OpenUrlCrossRef
    1. Jan Y. N.,
    2. Jan L. Y.
    (1993) HLH proteins, fly neurogenesis and vertebrate myogenesis. Cell 75, 827–830
    OpenUrlCrossRefPubMedWeb of Science
    1. Johnson J. E.,
    2. Gartside C. L.,
    3. Jaynes J. B.,
    4. Hauschka S. D.
    (1989) Expression of a transfected mouse muscle-creatine kinase gene is induced upon growth factor deprivation of myogenic but not of non myogenic cells. Dev. Biol 134, 258–62
    OpenUrlCrossRefPubMedWeb of Science
    1. Kidd S.,
    2. Baylies M. K.,
    3. Gasic G. P.,
    4. Young M. W.
    (1989) Structure and distribution of the Notch protein in developing Drosophila. Genes Dev. 3, 1113–1129. [published erratum appears in. Genes Dev 3, (1989)(12A):2020]
    OpenUrl
    1. Kodoyianni V.,
    2. Maine E. M.,
    3. Kimble J.
    (1992) Molecular basis of loss-of-function mutations in the glp-1 gene of Caenorhabditis elegans. Mol. Biol. of the Cell 3, 1199–1213
    OpenUrlAbstract/FREE Full Text
    1. Kooh P. J.,
    2. Fehon R. G.,
    3. Muskavitch M. A.
    (1993) Implication of dynamic patterns of Delta and Notch expression for cellular interactions during Drosophila development. Development 117, 493–507
    OpenUrlAbstract
    1. Kopan R.,
    2. Weintraub H.
    (1993) Mouse notch: expression in hair follicles correlates with cell fate determination. J. Cell Biol 121, 631–41
    OpenUrlAbstract/FREE Full Text
    1. LaMarco K.,
    2. Thompson C. C.,
    3. Byers B. P.,
    4. Walton E. M.,
    5. McKnight S. L.
    (1991) Identification of Ets-and Notch-related subunits in GA binding protein. Science 253, 789–792
    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. Lieber T.,
    2. Wesley C. S.,
    3. Alcamo E.,
    4. Hassel B.,
    5. Krane J. F.,
    6. Campos-Ortega J. A.,
    7. Young M. W.
    (1992) Single amino acid substitutions in EGF-like elements of Notch and Delta modify Drosophila development and affect cell adhesion in vitro. Neuron 9, 847–859
    OpenUrlCrossRefPubMedWeb of Science
    1. Lyman D.,
    2. Young M. W.
    (1993) Further evidence for function of the Drosophila Notch protein as a transmembrane receptor. Proc. Natl. Acad. Sci. USA 90, 10395–10399
    OpenUrlAbstract/FREE Full Text
    1. Mango S. E.,
    2. Maine E. M.,
    3. Kimble J.
    (1991) Carboxy-terminal truncation activates glp-1 protein to specify vulval fates in Caenorhabditis elegans. Nature 352, 811–815
    OpenUrlCrossRefPubMed
    1. Miner J. H.,
    2. Wold B.
    (1990) Herculin, a fourth member of the MyoD family of myogenic regulatory genes. Proc. Natl. Acad. Sci. USA 87, 1089–1093
    OpenUrlAbstract/FREE Full Text
    1. Moore W. J.,
    2. Mintz B.
    (1972) Clonal model of vertebral column and skull development derived from genetically mosaic skeletons in allophenic mice. Dev. Biol 27, 55–70
    OpenUrlCrossRefPubMed
    1. Murre C.,
    2. McCaw P. S.,
    3. Vassin H.,
    4. Caudy M.,
    5. Jan L. Y.,
    6. Jan Y. N.,
    7. Cabrera C. V.,
    8. Buskin J. M.,
    9. Hauschka S. D.,
    10. Lassar A. B.,
    11. Weintraub H.,
    12. Baltimor D.
    (1989) Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell 58, 537–544
    OpenUrlCrossRefPubMedWeb of Science
    1. Nye J. S.,
    2. Kopan R.,
    3. Axel R.
    (1994) An activated Notch suppresses neurogenesis and myogenesis but not gliogenesis in mammalian cells. Development 120, 2421–2430
    OpenUrlAbstract/FREE Full Text
    1. Neuhold L. A.,
    2. Wold B.
    (1993) HLH forced dimers: tethering MyoD to E47 generates a dominant positive myogenic factor insulated from negative regulation by Id. Cell 74, 1033–1044
    OpenUrlCrossRefPubMedWeb of Science
    1. Ordahl C. P.,
    2. Le Douarin N. M.
    (1992) Two myogenic lineages within the developing somite. Development 114, 339–353
    OpenUrlAbstract
    1. Ott M. O.,
    2. Bober E.,
    3. Lyons G.,
    4. Arnold H. H.,
    5. Buckingham M.
    (1991) Early expression of the myogenic regulatory, Myf-5, in precursor cells of skeletal muscle in the mouse embryo. Development 111, 1097–1107
    OpenUrlAbstract/FREE Full Text
    1. Pownall M. E.,
    2. Emerson C., Jr
    (1992) Sequential activation of three myogenic regulatory genes during somite morphogenesis in quail embryos. Dev. Biol 151, 67–79
    OpenUrlCrossRefPubMedWeb of Science
    1. Reaume A. G.,
    2. Conlon R. A.,
    3. Zirngibl R.,
    4. Yamaguchi T. P.,
    5. Rossant J.
    (1992) Expression analysis of a Notch homologue in the mouse embryo. Dev. Biol 154, 377–87
    OpenUrlCrossRefPubMedWeb of Science
    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. Rechsteiner M.
    (1988) Regulation of enzyme levels by proteolysis: the role of pest regions. Advances In Enzyme Regulation 27, 135–151
    OpenUrlCrossRefPubMedWeb of Science
    1. Roehl H.,
    2. Kimbel J.
    (1993) Control of cell fate in C. elegans by a GLP-1 peptide consisting primarily of ankyrin repeats. Nature 364, 632–635
    OpenUrlCrossRefPubMed
    1. Rong P. M.,
    2. Teillet M.-A.,
    3. Ziller C.,
    4. Le Douarin N. M.
    (1992) The neural tube/notochord complex is necessary for vertebral but not limb and body wall striated muscle differentition. Development 115, 657–672
    OpenUrlAbstract/FREE Full Text
    1. Roth M. B.,
    2. Zahler A.,
    3. Stolk J. H.
    (1991) A conserved family of nuclear phsphoproteins localized to sites of polymerase II transcription. J. Cell Biol 115, 587–596
    OpenUrlAbstract/FREE Full Text
    1. Rudnicki M. A.,
    2. Schnegelsberg P. N. J.,
    3. Stead R. H.,
    4. Braun T.,
    5. Arnold H. H.,
    6. Jaenisch R.
    (1993) MyoD or Myf-5 is required for the formation of skeletal muscle. Cell 75, 1351–1359
    OpenUrlCrossRefPubMedWeb of Science
    1. Ruohola H.,
    2. Bremer K. A.,
    3. Baker D.,
    4. Swedlow J. R.,
    5. Jan L. Y.,
    6. Jan Y. N.
    (1991) Role of neurogenic genes in establishment of follicle cell fate and oocyte polarity during oogenesis in Drosophila. Cell 66, 433–449
    OpenUrlCrossRefPubMedWeb of Science
    1. Ruohola-Baker H.,
    2. Jan L. Y.,
    3. Jan Y. N.
    (1994) The role of gene cassettes in axis formation during Drosophila oogenesis. Trends in Genetics 10, 89–94
    OpenUrlCrossRefPubMedWeb of Science
    1. Rupp R. A.,
    2. Weintraub H.
    (1991) Ubiquitous MyoD transcription at the midblastula transition precedes induction-dependent MyoD expression in presumptive mesoderm of X. laevis. Cell 65, 927–937
    OpenUrlCrossRefPubMedWeb of Science
    1. Sassoon D.,
    2. Lyons G.,
    3. Wright W. E.,
    4. Lin V.,
    5. Lassar A.,
    6. Weintraub H.,
    7. Buckingham M.
    (1989) Expression of two myogenic regulatory factors myogenin and MyoD1 during mouse embryogenesis. Nature 341, 303–307
    OpenUrlCrossRefPubMed
    1. Shaknovich R.,
    2. Shue G.,
    3. Kohtz D. S.
    (1992) Conformational activation of a basic helix-loop-helix protein (MyoD1) by the C-terminal region of murine HSP90 (HSP84). Molec. Cell. Biol 12, 5059–5068
    OpenUrlAbstract/FREE Full Text
    1. Sidorova J.,
    2. Breeden L.
    (1993) Analysis of the SW14/SW16 protein complex, which directs G1/S-specific transcription in Saccharomyces cerevisiae. Molec. Cell. Biol 13, 1069–1077
    OpenUrlAbstract/FREE Full Text
    1. Skeath J. B.,
    2. Carroll S. B.
    (1991) Regulation of achaete-scute gene expression and sensory organ pattern formation in the Drosophila wing. Genes Dev 5, 984–995
    OpenUrlAbstract/FREE Full Text
    1. Skeath J. B.,
    2. Carroll S. B.
    (1992) Regulation of proneural gene expression and cell fate during neuroblast segregation in the Drosophila embryo. Development 114, 939–946
    OpenUrlAbstract
    1. Stern C. D.,
    2. Fraser S. E.,
    3. Keynes R. J.,
    4. Primmett D. R.
    (1988) A cell lineage analysis of segmentation in the chick embryo. Development 104, 231–244
    OpenUrlAbstract/FREE Full Text
    1. Sternberg P. W.
    (1988) Lateral inhibition during vulval induction in Caenorhabditis elegans. Nature 335, 551–554
    OpenUrlCrossRefPubMedWeb of Science
    1. Stifani S.,
    2. Blaumuller C. M.,
    3. Redhead N. J.,
    4. Hill R. E.,
    5. Artavanis-Tsakonas S.
    (1992) Human homologs of a Drosophila Enhancer of split gene product define a novel family of nuclear proteins. Nature Genet 2, 119–127
    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. Swiatek P. J.,
    2. Lindsell C. E.,
    3. Franco Del Amo F.,
    4. Weinmaster G.,
    5. Gridley T.
    (1994) Notch1 is essential for postimplantation development in mice. Genes Dev 8, 707–719
    OpenUrlAbstract/FREE Full Text
    1. Tam P. L.,
    2. Meier S.,
    3. Jacobson G. A.
    (1982) Differentiation of the metameric pattern in the embryonic axis of the mouse. Differentiation 21, 109–122
    OpenUrlCrossRefPubMedWeb of Science
    1. Tam P. L.
    (1988) The allocation of cells in the presomitic mesoderm during somite segmentation in the mouse embryo. Development 103, 379–390
    OpenUrlAbstract
    1. Tapscott S. J.,
    2. Thayer M. J.,
    3. Weintraub H.
    (1993) Deficiency in rhabdomyosarcomas of a factor required for MyoD activity and myogenesis. Science 259, 1450–1453
    OpenUrlAbstract/FREE Full Text
    1. Tapscott S. J.,
    2. Davis R. L.,
    3. Thayer M. J.,
    4. Cheng P. F.,
    5. Weintraub H.,
    6. Lassar A. B.
    (1988) MyoD1: a nuclear phosphoprotein requiring a Myc homology region to convert fibroblasts to myoblasts. Science 242, 405–411
    OpenUrlAbstract/FREE Full Text
    1. Villares R.,
    2. Cabrera C. V.
    (1987) The achaete-scute gene complex of D. melanogaster: conserved domains in a subset of genes required for neurogenesis and their homology to Myc. Cell 50, 415–424
    OpenUrlCrossRefPubMedWeb of Science
    1. Weinmaster G.,
    2. Roberts V. J.,
    3. Lemke G.
    (1992) Notch2: a second mammalian Notch gene. Development 116, 931–941
    OpenUrlAbstract/FREE Full Text
    1. Weinmaster G.,
    2. Roberts V. J.,
    3. Lemke G.
    (1991) A homolog of DrosophilaNotch expressed during mammalian development. Development 113, 199–205
    OpenUrlAbstract
    1. Weintraub H.
    (1993) The MyoD family and myogenesis: redundancy, networks, and thresholds. Cell 75, 1241–1244
    OpenUrlCrossRefPubMedWeb of Science
    1. Weintraub H.,
    2. Davis R.,
    3. Tapscott S.,
    4. Thayer M.,
    5. Krause M.,
    6. Benezra R.,
    7. Blackwell T. K.,
    8. Turner D.,
    9. Rupp R.,
    10. Hollenberg S.,
    11. Zhuang Y.,
    12. Lassar A.
    (1990) The MyoD gene family: nodal point during specification of the muscle cell lineage. Science 251, 761–766
    OpenUrl
    1. Weintraub H.,
    2. Dwarki V. J.,
    3. Verma I.,
    4. Davis R.,
    5. Hollenberg S.,
    6. Snider L.,
    7. Lassar A.,
    8. Tapscott S.
    (1991) Muscle specific activation by MyoD. Genes Dev 5, 1377–1386
    OpenUrlAbstract/FREE Full Text
    1. Williams B. A.,
    2. Ordahl C. P.
    (1994) Pax-3 expression in the segmental mesoderm marks early stages in myogenic cell specification. Development 120, 785–796
    OpenUrlAbstract
    1. Yochem J.,
    2. Greenwald I.
    (1989) glp-1 and lin-12, genes implicated in distinct cell-cell interactions in C. elegans, encode similar transmembrane proteins. Cell 58, 553–563
    OpenUrlCrossRefPubMedWeb of Science
Back to top

 Download PDF

Email
JOURNAL ARTICLES
The intracellular domain of mouse Notch: a constitutively activated repressor of myogenesis directed at the basic helix-loop-helix region of MyoD
R. Kopan, J.S. Nye, H. Weintraub
Development 1994 120: 2385-2396;
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