International Journal of Hematology

, Volume 75, Issue 5, pp 449–459 | Cite as

The Notch Pathway: Modulation of Cell Fate Decisions in Hematopoiesis

Progress in Hematology

Abstract

The hematopoietic system is maintained by a rare population of hematopoietic stem cells (HSC) that are thought to undergo self-renewal as well as continuously produce progeny that differentiate into the various hematopoietic lineages. However, the mechanisms regulating cell fate choices by HSC and their progeny have not been understood. Results of most studies support a stochastic model of cell fate determination in which growth factors support only the survival or proliferation of the progeny specified along a particular lineage. In other developmental systems, however, Notch signaling has been shown to play a central role in regulating fate decisions of numerous types of precursors, often inhibiting a particular (default) pathway while permitting self-renewal or differentiation along an alternative pathway. There is also accumulating evidence that the Notch pathway affects survival, proliferation, and cell fate choices at various stages of hematopoietic cell development, including the decisions of HSC to self-renew or differentiate and of common lymphoid precursors to undergo T- or B-cell differentiation. These data suggest that the Notch pathway plays a fundamental role in the development and maintenance of the hematopoietic system.

Key words

Notch Cell fate Hematopoiesis Stem cells T-lymphocyte 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development.Science. 1999; 284:770–776.PubMedGoogle Scholar
  2. 2.
    Greenwald I. LIN-12/Notch signaling: lessons from worms and flies.Genes Dev. 1998;12:1751–1762.PubMedGoogle Scholar
  3. 3.
    Moohr OL.Genetics. 1919;4:252.Google Scholar
  4. 4.
    Poulson DF. The effect of certain X-chromosome deficiencies in the embryonic development ofDrosophila melanogaster.J Exp Zool. 1940;83:271–325.Google Scholar
  5. 5.
    Bray S. A Notch affair.Cell. 1998;93:499–503.PubMedGoogle Scholar
  6. 6.
    Kidd S, Kelley MR, Young MW. Sequence of the notch locus of Drosophila melanogaster: relationship of the encoded protein to mammalian clotting and growth factors.Mol Cell Biol. 1986;6: 3094–3108.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Wharton KA, Johansen KM, Xu T, Artavanis-Tsakonas S. Nucleotide sequence from the neurogenic locus notch implies a gene product that shares homology with proteins containing EGF-like repeats.Cell. 1985;43:567–581.PubMedGoogle Scholar
  8. 8.
    Yochem J, Weston K, Greenwald I. The Caenorhabditis elegans lin-12 gene encodes a transmembrane protein with overall similarity to Drosophila Notch.Nature. 1988;335:547–550.PubMedGoogle Scholar
  9. 9.
    Yochem J, Greenwald I. glp-1 and lin-12, genes implicated in distinct cell-cell interactions in C. elegans, encode similar transmembrane proteins.Cell. 1989;58:553–563.PubMedGoogle Scholar
  10. 10.
    Ellisen LW, Bird J, West DC, et al. TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms.Cell. 1991;66:649–661.PubMedGoogle Scholar
  11. 11.
    Weinmaster G, Roberts VJ, Lemke G. A homolog of Drosophila Notch expressed during mammalian development.Development. 1991;113:199–205.PubMedGoogle Scholar
  12. 12.
    Weinmaster G, Roberts VJ, Lemke G. Notch2: a second mammalian Notch gene.Development. 1992;116:931–941.PubMedGoogle Scholar
  13. 13.
    Lardelli M, Dahlstrand J, Lendahl U. The novel Notch homologue mouse Notch 3 lacks specific epidermal growth factor-repeats and is expressed in proliferating neuroepithelium.Mech Dev. 1994;46: 123–136.PubMedGoogle Scholar
  14. 14.
    Uyttendaele H, Marazzi G, Wu G, Yan Q, Sassoon D, Kitajewski J. Notch4/int-3, a mammary proto-oncogene, is an endothelial cell-specific mammalian Notch gene.Development. 1996;122: 2251–2259.PubMedGoogle Scholar
  15. 15.
    Weinmaster G. The ins and outs of notch signaling.Mol Cell Neurosci. 1997;9:91–102.PubMedGoogle Scholar
  16. 16.
    Rebay I, Fleming RJ, Fehon RG, Cherbas L, Cherbas P, Artavanis-Tsakonas S. Specific EGF repeats of Notch mediate interactions with Delta and Serrate: implications for Notch as a multifunctional receptor.Cell. 1991;67:687–699.PubMedGoogle Scholar
  17. 17.
    de Celis JF, Barrio R, del Arco A, Garcia-Bellido A. Genetic and molecular characterization of a Notch mutation in its Delta- and Serrate-binding domain in Drosophila.Proc Natl Acad Sci U S A. 1993;90:4037–4041.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Greenwald I, Seydoux G. Analysis of gain-of-function mutations of the lin-12 gene of Caenorhabditis elegans.Nature. 1990;346: 197–199.PubMedGoogle Scholar
  19. 19.
    Fortini ME, Artavanis-Tsakonas S. The suppressor of hairless protein participates in notch receptor signaling.Cell. 1994;79:273–282.PubMedGoogle Scholar
  20. 20.
    Tani S, Kurooka H, Aoki T, Hashimoto N, Honjo T. The N- and C-terminal regions of RBP-J interact with the ankyrin repeats of Notch1 RAMIC to activate transcription.Nucleic Acids Res. 2001; 29:1373–1380.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Matsuno K, Diederich RJ, Go MJ, Blaumueller CM, Artavanis-Tsakonas S. Deltex acts as a positive regulator of Notch signaling through interactions with the Notch ankyrin repeats.Development. 1995;121:2633–2644.PubMedGoogle Scholar
  22. 22.
    Wu L, Aster JC, Blacklow SC, Lake R, Artavanis-Tsakonas S, Griffin JD. MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors.Nat Genet. 2000;26:484–489.PubMedGoogle Scholar
  23. 23.
    Kopan R, Nye JS, Weintraub H. The intracellular domain of mouse Notch: a constitutively activated repressor of myogenesis directed at the basic helix-loop-helix region of MyoD.Development. 1994; 120:2385–2396.PubMedGoogle Scholar
  24. 24.
    Rechsteiner M, Rogers SW. PEST sequences and regulation by proteolysis.Trends Biochem Sci. 1996;21:267–271.PubMedGoogle Scholar
  25. 25.
    Greenwald I. Structure/function studies of lin-12/Notch proteins.Curr Opin Genet Dev. 1994;4:556–562.PubMedGoogle Scholar
  26. 26.
    Logeat F, Bessia C, Brou C, et al. The Notch1 receptor is cleaved constitutively by a furin-like convertase.Proc Natl Acad Sci U S A. 1998;95:8108–8112.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Mumm JS, Kopan R. Notch signaling: from the outside in.Dev Biol. 2000;228:151–165.PubMedGoogle Scholar
  28. 28.
    Shimizu K, Chiba S, Kumano K, et al. Mouse jagged1 physically interacts with notch2 and other notch receptors.J Biol Chem. 1999; 274:32961–32969.PubMedGoogle Scholar
  29. 29.
    Lieber T, Wesley CS, Alcamo E, et al. Single amino acid substitutions in EGF-like elements of Notch and Delta modify Drosophila development and affect cell adhesion in vitro.Neuron. 1992;9: 847–859.PubMedGoogle Scholar
  30. 30.
    Fitzgerald K, Greenwald I. Interchangeability of Caenorhabditis elegans DSL proteins and intrinsic signalling activity of their extracellular domains in vivo.Development. 1995;121:4275–4282.PubMedGoogle Scholar
  31. 31.
    Henderson ST, Gao D, Christensen S, Kimble J. Functional domains of LAG-2, a putative signaling ligand for LIN-12 and GLP-1 receptors in Caenorhabditis elegans.Mol Biol Cell. 1997;8: 1751–1762.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Lindsell CE, Shawber CJ, Boulter J, Weinmaster G. Jagged: a mammalian ligand that activates Notch1.Cell. 1995;80:909–917.PubMedGoogle Scholar
  33. 33.
    Luo B, Aster JC, Hasserjian RP, Kuo F, Sklar J. Isolation and functional analysis of a cDNA for human Jagged2, a gene encoding a ligand for the Notch1 receptor.Mol Cell Biol. 1997;17:6057–6067.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Bettenhausen B, Hrabe de Angelis M, Simon D, Guenet JL, Gossler A. Transient and restricted expression during mouse embryogenesis of Dll1, a murine gene closely related to Drosophila Delta.Development. 1995;121:2407–2418.PubMedGoogle Scholar
  35. 35.
    Jen WC, Wettstein D, Turner D, Chitnis A, Kintner C. The Notch ligand, X-Delta-2, mediates segmentation of the paraxial meso-derm in Xenopus embryos.Development. 1997;124:1169–1178.PubMedGoogle Scholar
  36. 36.
    Dunwoodie SL, Henrique D, Harrison SM, Beddington RS. Mouse Dll3: a novel divergent Delta gene which may complement the function of other Delta homologues during early pattern formation in the mouse embryo.Development. 1997;124:3065–3076.PubMedGoogle Scholar
  37. 37.
    Shutter JR, Scully S, Fan W, et al. Dll4, a novel Notch ligand expressed in arterial endothelium.Genes Dev. 2000;14:1313–1318.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Fehon RG, Kooh PJ, Rebay I, et al. Molecular interactions between the protein products of the neurogenic loci Notch and Delta, two EGF-homologous genes in Drosophila.Cell. 1990;61:523–534.Google Scholar
  39. 39.
    Brown MS, Ye J, Rawson RB, Goldstein JL. Regulated intramem-brane proteolysis: a control mechanism conserved from bacteria to humans.Cell. 2000;100:391–398.Google Scholar
  40. 40.
    Parks AL, Klueg KM, Stout JR, Muskavitch MA. Ligand endocy-tosis drives receptor dissociation and activation in the Notch pathway.Development. 2000;127:1373–1385.PubMedGoogle Scholar
  41. 41.
    Mumm JS, Schroeter EH, Saxena MT, et al. A ligand-induced extracellular cleavage regulates gamma-secretase-like proteolytic activation of Notch1.Mol Cell. 2000;5:197–206.PubMedGoogle Scholar
  42. 42.
    Brou C, Logeat F, Gupta N, et al. A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metallopro-tease TACE.Mol Cell. 2000;5:207–216.PubMedGoogle Scholar
  43. 43.
    Schroeter EH, Kisslinger JA, Kopan R. Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain.Nature. 1998;393:382–386.PubMedGoogle Scholar
  44. 44.
    Huppert SS, Le A, Schroeter EH, et al. Embryonic lethality in mice homozygous for a processing-deficient allele of Notch1.Nature. 2000;405:966–970.PubMedGoogle Scholar
  45. 45.
    Kopan R, Goate A. A common enzyme connects notch signaling and Alzheimer’s disease.Genes Dev. 2000;14:2799–2806.PubMedGoogle Scholar
  46. 46.
    Fortini ME. Notch and presenilin: a proteolytic mechanism emerges.Curr Opin Cell Biol. 2001;13:627–634.PubMedGoogle Scholar
  47. 47.
    Ling PD, Hsieh JJ, Ruf IK, Rawlins DR, Hayward SD. EBNA-2 upregulation of Epstein-Barr virus latency promoters and the cellular CD23 promoter utilizes a common targeting intermediate, CBF1.J Virol. 1994;68:5375–5383.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Tun T, Hamaguchi Y, Matsunami N, Furukawa T, Honjo T, Kawaichi M. Recognition sequence of a highly conserved DNA binding protein RBP-J kappa.Nucleic Acids Res. 1994;22:965–971.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Kao HY, Ordentlich P, Koyano-Nakagawa N, et al. A histone deacetylase corepressor complex regulates the Notch signal trans-duction pathway.Genes Dev. 1998;12:2269–2277.PubMedPubMedCentralGoogle Scholar
  50. 50.
    Zhou S, Fujimuro M, Hsieh JJ, et al. SKIP, a CBF1-associated protein, interacts with the ankyrin repeat domain of NotchIC to facilitate NotchIC function.Mol Cell Biol. 2000;20:2400–2410.PubMedPubMedCentralGoogle Scholar
  51. 51.
    Zhou S, Hayward SD. Nuclear localization of CBF1 is regulated by interactions with the SMRT corepressor complex.Mol Cell Biol. 2001;21:6222–6232.PubMedPubMedCentralGoogle Scholar
  52. 52.
    Hsieh JJ, Zhou S, Chen L, Young DB, Hayward SD. CIR, a core-pressor linking the DNA binding factor CBF1 to the histone deacetylase complex.Proc Natl Acad Sci U S A. 1999;96:23–28.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Taniguchi Y, Furukawa T, Tun T, Han H, Honjo T. LIM protein KyoT2 negatively regulates transcription by association with the RBP-J DNA-binding protein.Mol Cell Biol. 1998;18:644–654.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Petcherski AG, Kimble J. LAG-3 is a putative transcriptional activator in the C. elegans Notch pathway.Nature. 2000;405:364–368.PubMedGoogle Scholar
  55. 55.
    Doyle TG, Wen C, Greenwald I. SEL-8, a nuclear protein required for LIN-12 and GLP-1 signaling in Caenorhabditis elegans.Proc Natl Acad Sci U S A. 2000;97:7877–7881.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Kitagawa M, Oyama T, Kawashima T, et al. A human protein with sequence similarity to Drosophila mastermind coordinates the nuclear form of notch and a CSL protein to build a transcriptional activator complex on target promoters.Mol Cell Biol. 2001;21: 4337–4346.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Petcherski AG, Kimble J. Mastermind is a putative activator for Notch.Curr Biol. 2000;10:R471–473.PubMedGoogle Scholar
  58. 58.
    Schuldt AJ, Brand AH. Mastermind acts downstream of notch to specify neuronal cell fates in the Drosophila central nervous system.Dev Biol. 1999;205:287–295.PubMedGoogle Scholar
  59. 59.
    Kurooka H, Honjo T. Functional interaction between the mouse notch1 intracellular region and histone acetyltransferases PCAF and GCN5.J Biol Chem. 2000;275:17211–17220.PubMedGoogle Scholar
  60. 60.
    Jarriault S, Le Bail O, Hirsinger E, et al. Delta-1 activation of notch-1 signaling results in HES-1 transactivation.Mol Cell Biol. 1998;18:7423–7431.PubMedPubMedCentralGoogle Scholar
  61. 61.
    Kuroda K, Tani S, Tamura K, Minoguchi S, Kurooka H, Honjo T. Delta-induced Notch signaling mediated by RBP-J inhibits MyoD expression and myogenesis.J Biol Chem. 1999;274:7238–7244.PubMedGoogle Scholar
  62. 62.
    Jarriault S, Brou C, Logeat F, Schroeter EH, Kopan R, Israel A. Signalling downstream of activated mammalian Notch.Nature. 1995; 377:355–358.PubMedGoogle Scholar
  63. 63.
    Kageyama R, Ohtsuka T, Tomita K. The bHLH gene Hes1 regulates differentiation of multiple cell types.Mol Cells. 2000;10:1–7.PubMedGoogle Scholar
  64. 64.
    Hirsinger E, Malapert P, Dubrulle J, et al. Notch signalling acts in postmitotic avian myogenic cells to control MyoD activation.Development. 2001;128:107–116.PubMedGoogle Scholar
  65. 65.
    Ordentlich, P, Lin A, Shen CP, et al. Notch inhibition of E47 supports the existence of a novel signaling pathway.Mol Cell Biol. 1998;18:2230–2239.PubMedPubMedCentralGoogle Scholar
  66. 66.
    Matsuno K, Eastman D, Mitsiades T, et al. Human deltex is a conserved regulator of Notch signalling.Nat Genet. 1998;19:74–78.PubMedGoogle Scholar
  67. 67.
    Kishi N, Tang Z, Maeda Y, et al. Murine homologs of deltex define a novel gene family involved in vertebrate Notch signaling and neurogenesis.Int J Dev Neurosci. 2001;19:21–35.PubMedGoogle Scholar
  68. 68.
    Yamamoto N, Yamamoto S, Inagaki F, et al. Role of Deltex-1 as a transcriptional regulator downstream of the Notch receptor.J Biol Chem. 2001;276:45031–45040.PubMedGoogle Scholar
  69. 69.
    Kojika S, Griffin JD. Notch receptors and hematopoiesis.Exp Hematol. 2001;29:1041–1052.PubMedGoogle Scholar
  70. 70.
    Moloney DJ, Panin VM, Johnston SH, et al. Fringe is a glycosyl-transferase that modifies Notch.Nature. 2000;406:369–375.PubMedGoogle Scholar
  71. 71.
    Bruckner K, Perez L, Clausen H, Cohen S. Glycosyltransferase activity of Fringe modulates Notch-Delta interactions.Nature. 2000;406:411–415.PubMedGoogle Scholar
  72. 72.
    Ju BG, Jeong S, Bae E, et al. Fringe forms a complex with Notch.Nature. 2000;405:191–195.PubMedGoogle Scholar
  73. 73.
    Blair SS. Notch signaling: Fringe really is a glycosyltransferase.Curr Biol. 2000;10:R608–612.PubMedGoogle Scholar
  74. 74.
    Panin VM, Papayannopoulos V, Wilson R, Irvine KD. Fringe modulates Notch-ligand interactions.Nature. 1997;387:908–912.PubMedGoogle Scholar
  75. 75.
    Fleming RJ, Gu Y, Hukriede NA. Serrate-mediated activation of Notch is specifically blocked by the product of the gene fringe in the dorsal compartment of the Drosophila wing imaginal disc.Development. 1997;124:2973–2981.PubMedGoogle Scholar
  76. 76.
    Laufer E, Dahn R, Orozco OE, et al. Expression of Radical fringe in limb-bud ectoderm regulates apical ectodermal ridge formation.Nature. 1997;386:366–373.PubMedGoogle Scholar
  77. 77.
    Cohen B, Bashirullah A, Dagnino L, et al. Fringe boundaries coincide with Notch-dependent patterning centres in mammals and alter Notch-dependent development in Drosophila.Nat Genet. 1997;16:283–288.PubMedGoogle Scholar
  78. 78.
    Hicks C, Johnston SH, diSibio G, Collazo A, Vogt TF, Weinmaster G. Fringe differentially modulates Jagged1 and Delta1 signalling through Notch1 and Notch2.Nat Cell Biol. 2000;2:515–520.PubMedGoogle Scholar
  79. 79.
    Yedvobnick B, Smoller D, Young P, Mills D. Molecular analysis of the neurogenic locus mastermind of Drosophila melanogaster.Genetics. 1998;118:483–497.Google Scholar
  80. 80.
    Xu T, Rebay I, Fleming RJ, Scottgale TN, Artavanis-Tsakonas S. The Notch locus and the genetic circuitry involved in early Drosophila neurogenesis.Genes Dev. 1990;4:464–475.PubMedGoogle Scholar
  81. 81.
    Helms W, Lee H, Ammerman M, Parks AL, Muskavitch MA, Yed-vobnick B. Engineered truncations in the Drosophila mastermind protein disrupt Notch pathway function.Dev Biol. 1999;215: 358–374.PubMedGoogle Scholar
  82. 82.
    Rijsewijk F, Schuermann M, Wagenaar E, Parren P, Weigel D, Nusse R. The Drosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless.Cell. 1987;50:649–657.PubMedGoogle Scholar
  83. 83.
    Axelrod JD, Matsuno K, Artavanis-Tsakonas S, Perrimon N. Interaction between Wingless and Notch signaling pathways mediated by dishevelled.Science. 1996;271:1826–1832.PubMedGoogle Scholar
  84. 84.
    Phillips RG, Whittle JR. Wingless expression mediates determination of peripheral nervous system elements in late stages of Drosophila wing disc development.Development. 1993;118: 427–438.PubMedGoogle Scholar
  85. 85.
    Fanto M, Mlodzik M. Asymmetric Notch activation specifies pho-toreceptors R3 and R4 and planar polarity in the Drosophila eye.Nature. 1999;397:523–526.PubMedGoogle Scholar
  86. 86.
    Stifani S, Blaumueller CM, Redhead NJ, Hill RE, Artavanis-Tsakonas S. Human homologs of a Drosophila Enhancer of Split gene product define a novel family of nuclear proteins.Nat Genet. 1992;2:119–127.PubMedGoogle Scholar
  87. 87.
    Chen G, Courey AJ. Groucho/TLE family proteins and transcriptional repression.Gene. 2000;249:1–16.PubMedGoogle Scholar
  88. 88.
    Grbavec D, Stifani S. Molecular interaction between TLE1 and the carboxyl-terminal domain of HES-1 containing the WRPW motif.Biochem Biophys Res Commun. 1996;223:701–705.PubMedGoogle Scholar
  89. 89.
    Fisher AL, Caudy M. Groucho proteins: transcriptional corepressors for specific subsets of DNA-binding transcription factors in vertebrates and invertebrates.Genes Dev. 1998;12:1931–1940.PubMedGoogle Scholar
  90. 90.
    Fisher AL, Ohsako S, Caudy M. The WRPW motif of the hairy-related basic helix-loop-helix repressor proteins acts as a 4-amino-acid transcription repression and protein-protein interaction domain.Mol Cell Biol. 1996;16:2670–2677.PubMedPubMedCentralGoogle Scholar
  91. 91.
    Paroush Z, Finley RL Jr, Kidd T, et al. Groucho is required for Drosophila neurogenesis, segmentation, and sex determination and interacts directly with hairy-related bHLH proteins.Cell. 1994; 79:805–815.PubMedGoogle Scholar
  92. 92.
    Heitzler P, Bourouis M, Ruel L, Carteret C, Simpson P. 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;122:161–171.PubMedGoogle Scholar
  93. 93.
    Javed A, Guo B, Hiebert S, et al. Groucho/TLE/R-esp proteins associate with the nuclear matrix and repress RUNX (CBF(alpha)/AML/PEBP2(alpha)) dependent activation of tissue-specific gene transcription.J Cell Sci.. 2000;113:2221–2231.PubMedGoogle Scholar
  94. 94.
    Imai Y, Kurokawa M, Tanaka K, et al. TLE, the human homolog of groucho, interacts with AML1 and acts as a repressor of AML1-induced transactivation.Biochem Biophys Res Commun.. 1998;252: 582–589.PubMedGoogle Scholar
  95. 95.
    Levanon D, Goldstein RE, Bernstein Y, et al. Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors.Proc Natl Acad Sci U S A. 1998;95:11590–11595.PubMedPubMedCentralGoogle Scholar
  96. 96.
    Eberhard D, Jimenez G, Heavey B, Busslinger M. Transcriptional repression by Pax5 (BSAP) through interaction with corepressors of the Groucho family.EMBO J. 2000;19:2292–2303.PubMedPubMedCentralGoogle Scholar
  97. 97.
    Nutt SL, Eberhard D, Horcher M, Rolink AG, Busslinger M. Pax5 determines the identity of B cells from the beginning to the end of B-lymphopoiesis.Int Rev Immunol. 2001;20:65–82.PubMedGoogle Scholar
  98. 98.
    Wilkinson HA, Fitzgerald K, Greenwald I. 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. 1994;79:1187–1198.PubMedGoogle Scholar
  99. 99.
    Seydoux G, Greenwald I. Cell autonomy of lin-12 function in a cell fate decision in C. elegans.Cell. 1989;57:1237–1245.PubMedGoogle Scholar
  100. 100.
    Uemura T, Shepherd S, Ackerman L, Jan LY, Jan YN. Numb, a gene required in determination of cell fate during sensory organ formation in Drosophila embryos.Cell. 1989;58:349–360.PubMedGoogle Scholar
  101. 101.
    Frise E, Knoblich JA, Younger-Shepherd S, Jan LY, Jan YN. The Drosophila Numb protein inhibits signaling of the Notch receptor during cell-cell interaction in sensory organ lineage.Proc Natl Acad Sci U S A. 1996;93:11925–11932.PubMedPubMedCentralGoogle Scholar
  102. 102.
    Henderson ST, Gao D, Lambie EJ, Kimble J. Lag-2 may encode a signaling ligand for the GLP-1 and LIN-12 receptors of C. elegans.Development. 1994;120:2913–2924.PubMedGoogle Scholar
  103. 103.
    Crittenden SL, Troemel ER, Evans TC, Kimble J. GLP-1 is localized to the mitotic region of the C. elegans germ line.Development. 1994;120:2901–2911.PubMedGoogle Scholar
  104. 104.
    Berry LW, Westlund B, Schedl T. Germ-line tumor formation caused by activation of glp-1, a Caenorhabditis elegans member of the Notch family of receptors.Development. 1997;124:925–936.PubMedGoogle Scholar
  105. 105.
    Nishikawa SI, Nishikawa S, Hirashima M, Matsuyoshi N, Kodama H. Progressive lineage analysis by cell sorting and culture identifies FLK1+VE-cadherin+ cells at a diverging point of endothelial and hemopoietic lineages.Development. 1998;125:1747–1757.PubMedGoogle Scholar
  106. 106.
    Choi K, Kennedy M, Kazarov A, Papadimitriou JC, Keller G. A common precursor for hematopoietic and endothelial cells.Development. 1998;125:725–732.PubMedGoogle Scholar
  107. 107.
    Suda T, Takakura N, Oike Y. Hematopoiesis and angiogenesis.Int J Hematol. 2000;71:99–107.PubMedGoogle Scholar
  108. 108.
    Takakura N, Watanabe T, Suenobu S, et al. A role for hematopoietic stem cells in promoting angiogenesis.Cell. 2000;102:199–209.PubMedPubMedCentralGoogle Scholar
  109. 109.
    Swiatek PJ, Lindsell CE, del Amo FF, Weinmaster G, Gridley T. Notch1 is essential for postimplantation development in mice.Genes Dev. 1994;8:707–719.PubMedGoogle Scholar
  110. 110.
    Conlon RA, Reaume AG, Rossant J. Notch1 is required for the coordinate segmentation of somites.Development. 1995;121: 1533–1545.PubMedGoogle Scholar
  111. 111.
    Krebs LT, Xue Y, Norton CR, et al. Notch signaling is essential for vascular morphogenesis in mice.Genes Dev. 2000;14:1343–1352.PubMedPubMedCentralGoogle Scholar
  112. 112.
    Xue Y, Gao X, Lindsell CE, et al. Embryonic lethality and vascular defects in mice lacking the Notch ligand Jagged1.Hum Mol Genet. 1999;8:723–730.PubMedGoogle Scholar
  113. 113.
    Jiang R, Lan Y, Chapman HD, et al. Defects in limb, craniofacial, and thymic development in Jagged2 mutant mice.Genes Dev. 1998;12:1046–1057.PubMedPubMedCentralGoogle Scholar
  114. 114.
    Walker L, Carlson A, Tan-Pertel HT, Weinmaster G, Gasson J. The Notch receptor and its ligands are selectively expressed during hematopoietic development in the mouse.Stem Cells. 2001;19: 543–552.PubMedGoogle Scholar
  115. 115.
    Gridley T. Notch signaling during vascular development.Proc Natl Acad Sci U S A. 2001;98:5377–5378.PubMedPubMedCentralGoogle Scholar
  116. 116.
    Risau W. Mechanisms of angiogenesis.Nature. 1997;386:671–674.PubMedPubMedCentralGoogle Scholar
  117. 117.
    Beck L Jr, D’Amore PA. Vascular development: cellular and molecular regulation.FASEB J. 1997;11:365–373.PubMedGoogle Scholar
  118. 118.
    Del Amo FF, Smith DE, Swiatek PJ, et al. Expression pattern of Motch, a mouse homolog of Drosophila Notch, suggests an important role in early postimplantation mouse development.Development. 1992;115:737–744.PubMedGoogle Scholar
  119. 119.
    Reaume AG, Conlon RA, Zirngibl R, Yamaguchi TP, Rossant J. Expression analysis of a Notch homologue in the mouse embryo.Dev Biol. 1992;154:377–387.PubMedGoogle Scholar
  120. 120.
    Villa N, Walker L, Lindsell CE, Gasson J, Iruela-Arispe ML, Wein-master G. Vascular expression of Notch pathway receptors and ligands is restricted to arterial vessels.Mech Dev. 2001;108:161–164.PubMedGoogle Scholar
  121. 121.
    Joutel A, Andreux F, Gaulis S, et al. The ectodomain of the Notch3 receptor accumulates within the cerebrovasculature of CADASIL patients.J Clin Invest. 2000;105:597–605.PubMedPubMedCentralGoogle Scholar
  122. 122.
    Shirayoshi Y, Yuasa Y, Suzuki T, et al. Proto-oncogene of int-3, a mouse Notch homologue, is expressed in endothelial cells during early embryogenesis.Genes Cells. 1997;2:213–224.PubMedGoogle Scholar
  123. 123.
    Myat A, Henrique D, Ish-Horowicz D, Lewis J. A chick homologue of Serrate and its relationship with Notch and Delta homologues during central neurogenesis.Dev Biol. 1996;174:233–247.PubMedGoogle Scholar
  124. 124.
    Hrabe de Angelis M, McIntyre J 2nd, Gossler A. Maintenance of somite borders in mice requires the Delta homologue DII1.Nature. 1997;386:717–721.PubMedGoogle Scholar
  125. 125.
    Uyttendaele H, Ho J, Rossant J, Kitajewski J. Vascular patterning defects associated with expression of activated Notch4 in embryonic endothelium.Proc Natl Acad Sci U S A. 2001;98:5643–5648.PubMedPubMedCentralGoogle Scholar
  126. 126.
    Lawson ND, Scheer N, Pham VN, et al. Notch signaling is required for arterial-venous differentiation during embryonic vascular development.Development. 2001;128:3675–3683.PubMedGoogle Scholar
  127. 127.
    Milner LA, Bigas A. Notch as a mediator of cell fate determination in hematopoiesis: evidence and speculation.Blood. 1999;93: 2431–2448.PubMedGoogle Scholar
  128. 128.
    Robson MacDonald H, Wilson A, Radtke F. Notch1 and T-cell development: insights from conditional knockout mice.Trends Immunol. 2001;22:155–160.Google Scholar
  129. 129.
    von Boehmer H. Coming to grips with Notch.J Exp Med. 2001;194:F43–46.Google Scholar
  130. 130.
    Robey E. Regulation of T cell fate by Notch.Annu Rev Immunol. 1999;17:283–295.PubMedGoogle Scholar
  131. 131.
    Osborne B, Miele L. Notch and the immune system.Immunity. 1999;11:653–663.PubMedGoogle Scholar
  132. 132.
    Aster JC, Pear WS. Notch signaling in leukemia.Curr Opin Hematol. 2001;8:237–244.PubMedGoogle Scholar
  133. 133.
    Pear WS, Aster JC, Scott ML, et al. Exclusive development of T cell neoplasms in mice transplanted with bone marrow expressing activated Notch alleles.J Exp Med. 1996;183:2283–2291.PubMedGoogle Scholar
  134. 134.
    Rohn JL, Lauring AS, Linenberger ML, Overbaugh J. Transduction of Notch2 in feline leukemia virus-induced thymic lymphoma.J Virol. 1996;70:8071–8080.PubMedPubMedCentralGoogle Scholar
  135. 135.
    Bellavia D, Campese AF, Alesse E, et al. Constitutive activation of NF-kappaB and T-cell leukemia/lymphoma in Notch3 transgenic mice.EMBO J. 2000;19:3337–3348.PubMedPubMedCentralGoogle Scholar
  136. 136.
    Yan XQ, Sarmiento U, Sun Y, et al. A novel Notch ligand, Dll4, induces T-cell leukemia/lymphoma when overexpressed in mice by retroviral-mediated gene transfer.Blood. 2001;98:3793–3799.PubMedGoogle Scholar
  137. 137.
    Milner LA, Kopan R, Martin DI, Bernstein ID. A human homologue of the Drosophila developmental gene, Notch, is expressed in CD34+ hematopoietic precursors.Blood. 1994;83:2057–2062.PubMedGoogle Scholar
  138. 138.
    Ohishi K, Varnum-Finney, B, Flowers D, Anasetti C, Myerson D, Bernstein ID. Monocytes express high amounts of Notch and undergo cytokine specific apoptosis following interaction with the Notch ligand, Delta-1.Blood. 2000;95:2847–2854.PubMedGoogle Scholar
  139. 139.
    Hasserjian RP, Aster JC, Davi F, Weinberg DS, Sklar J. Modulated expression of notch1 during thymocyte development.Blood. 1996;88:970–976.PubMedGoogle Scholar
  140. 140.
    Felli MP, Maroder M, Mitsiadis TA, et al. Expression pattern of notch1, 2 and 3 and Jagged1 and 2 in lymphoid and stromal thymus components: distinct ligand-receptor interactions in intrathymic T cell development.Int Immunol. 1999;11:1017–1025.PubMedGoogle Scholar
  141. 141.
    Bertrand FE, Eckfeldt CE, Lysholm AS, LeBien TW. Notch-1 and Notch-2 exhibit unique patterns of expression in human B-lineage cells.Leukemia. 2000;14:2095–2102.PubMedGoogle Scholar
  142. 142.
    Singh N, Phillips RA, Iscove NN, Egan SE. Expression of notch receptors, notch ligands, and fringe genes in hematopoiesis.Exp Hematol. 2000;28:527–534.PubMedGoogle Scholar
  143. 143.
    Jonsson JI, Xiang Z, Pettersson M, Lardelli M, Nilsson G. Distinct and regulated expression of Notch receptors in hematopoietic lineages and during myeloid differentiation.Eur J Immunol. 2001;31: 3240–3247.PubMedGoogle Scholar
  144. 144.
    Li L, Milner LA, Deng Y, et al. The human homolog of rat Jagged1 expressed by marrow stroma inhibits differentiation of 32D cells through interaction with Notch1.Immunity. 1998;8:43–55.PubMedGoogle Scholar
  145. 145.
    Jones P, May G, Healy L, et al. Stromal expression of Jagged 1 promotes colony formation by fetal hematopoietic progenitor cells.Blood. 1998;92:1505–1511.PubMedGoogle Scholar
  146. 146.
    Varnum-Finney B, Purton LE, Yu M, et al. The Notch ligand, Jagged-1, influences the development of primitive hematopoietic precursor cells.Blood. 1998;91:4084–4091.PubMedGoogle Scholar
  147. 147.
    Walker L, Lynch M, Silverman S, et al. The Notch/Jagged pathway inhibits proliferation of human hematopoietic progenitors in vitro.Stem Cells. 1999;17:162–171.PubMedGoogle Scholar
  148. 148.
    Anderson G, Pongracz J, Parnell S, Jenkinson, EJ. Notch ligand-bearing thymic epithelial cells initiate and sustain Notch signaling in thymocytes independently of T cell receptor signaling.Eur J Immunol. 2001;31:3349–3354.PubMedGoogle Scholar
  149. 149.
    Varnum-Finney B, Xu L, Brashem-Stein C, et al. Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling.Nat Med. 2000;6:1278–1281.PubMedGoogle Scholar
  150. 150.
    Han W, Ye Q, Moore MA. A soluble form of human Delta-like-1 inhibits differentiation of hematopoietic progenitor cells.Blood. 2000;95:1616–1625.PubMedGoogle Scholar
  151. 151.
    Tsai S, Fero J, Bartelmez S. Mouse Jagged2 is differentially expressed in hematopoietic progenitors and endothelial cells and promotes the survival and proliferation of hematopoietic progenitors by direct cell-to-cell contact.Blood. 2000;96:950–957.PubMedGoogle Scholar
  152. 152.
    Carlesso N, Aster JC, Sklar J, Scadden DT. Notch1-induced delay of human hematopoietic progenitor cell differentiation is associated with altered cell cycle kinetics.Blood. 1999;93:838–848.PubMedGoogle Scholar
  153. 153.
    Karanu FN, Murdoch B, Miyabayashi T, et al. Human homologues of Delta-1 and Delta-4 function as mitogenic regulators of primitive human hematopoietic cells.Blood. 2001;97:1960–1967.PubMedGoogle Scholar
  154. 154.
    Jaleco AC, Neves H, Hooijberg E, et al. Differential effects of notch ligands delta-1 and jagged-1 in human lymphoid differentiation.J Exp Med. 2001;194:991–1002.PubMedPubMedCentralGoogle Scholar
  155. 155.
    Karanu FN, Murdoch B, Gallacher L, et al. The Notch ligand jagged-1 represents a novel growth factor of human hematopoietic stem cells.J Exp Med. 2000;192:1365–1372.PubMedPubMedCentralGoogle Scholar
  156. 156.
    Pui JC, Allman D, Xu L, et al. Notch1 expression in early lymphopoiesis influences B versus T lineage determination.Immunity. 1999;11:299–308.PubMedGoogle Scholar
  157. 157.
    Wilson A, MacDonald HR, Radtke F. Notch 1-deficient common lymphoid precursors adopt a B cell fate in the thymus.J Exp Med. 2001;194:1003–1012.PubMedPubMedCentralGoogle Scholar
  158. 158.
    Radtke F, Wilson A, Stark G, et al. Deficient T cell fate specification in mice with an induced inactivation of Notch1.Immunity. 1999;10: 547–558.PubMedPubMedCentralGoogle Scholar
  159. 159.
    Tomita K, Hattori M, Nakamura, E, Nakanishi S, Minato N, Kageyama R. The bHLH gene Hes1 is essential for expansion of early T cell precursors.Genes Dev. 1999;13:1203–1210.PubMedPubMedCentralGoogle Scholar
  160. 160.
    Diederich RJ, Matsuno K, Hing H, Artavanis-Tsakonas S. Cytosolic interaction between deltex and Notch ankyrin repeats implicates deltex in the Notch signaling pathway.Development. 1994;120:473–481.Google Scholar
  161. 161.
    Zhuang Y, Soriano P, Weintraub H. The helix-loop-helix gene E2A is required for B cell formation.Cell. 1994;79:875–884.Google Scholar
  162. 162.
    Bain G, Robanus Maandag EC, te Riele HP, et al. Both E12 and E47 allow commitment to the B cell lineage.Immunity. 1997;6:145–154.Google Scholar
  163. 163.
    Engel I, Johns C, Bain G, Rivera RR, Murre C. Early thymocyte development is regulated by modulation of E2A protein activity.J Exp Med. 2001;194:733–745.PubMedPubMedCentralGoogle Scholar
  164. 164.
    Bain G, Quong MW, Soloff RS, Hedrick SM, Murre C. Thymocyte maturation is regulated by the activity of the helix-loop-helix protein, E47.J Exp Med. 1999;190:1605–1616.PubMedPubMedCentralGoogle Scholar
  165. 165.
    Washburn T, Schweighoffer E, Gridley T, et al. Notch activity influences the alphabeta versus gammadelta T cell lineage decision.Cell. 1997;88:833–843.PubMedGoogle Scholar
  166. 166.
    Robey E, Chang D, Itano A, et al. An activated form of Notch influences the choice between CD4 and CD8 T cell lineages.Cell. 1996;87:483–492.PubMedGoogle Scholar
  167. 167.
    Deftos ML, Huang E, Ojala EW, Forbush KA, Bevan MJ. Notch1 signaling promotes the maturation of CD4 and CD8 SP thymocytes.Immunity. 2000;13:73–84.PubMedPubMedCentralGoogle Scholar
  168. 168.
    Izon DJ, Punt JA, Xu L, et al. Notch1 regulates maturation of CD4+ and CD8+ thymocytes by modulating TCR signal strength.Immunity. 2001;14:253–264.PubMedGoogle Scholar
  169. 169.
    Jehn BM, Bielke W, Pear WS, Osborne BA. Cutting edge: protective effects of notch-1 on TCR-induced apoptosis.J Immunol. 1999;162:635–638.PubMedGoogle Scholar
  170. 170.
    Deftos ML, He YW, Ojala, EW, Bevan MJ. Correlating Notch signaling with thymocyte maturation.Immunity. 1998;9:777–786.PubMedPubMedCentralGoogle Scholar
  171. 171.
    Wolfer A, Bakker T, Wilson A, et al. Inactivation of Notch 1 in immature thymocytes does not perturb CD4 or CD8 T cell development.Nat Immunol. 2001;2:235–241.PubMedGoogle Scholar
  172. 172.
    Radtke F, Ferrero I, Wilson A, Lees R, Aguet M, MacDonald HR. Notch1 deficiency dissociates the intrathymic development of dendritic cells and T cells.J Exp Med. 2000;191:1085–1094.PubMedPubMedCentralGoogle Scholar
  173. 173.
    Milner LA, Bigas A, Kopan R, Brashem-Stein C, Bernstein ID, Martin DI. Inhibition of granulocytic differentiation by mNotch1.Proc Natl Acad Sci U S A. 1996;93:13014–13019.PubMedPubMedCentralGoogle Scholar
  174. 174.
    Bigas A, Martin DI, Milner LA. Notch1 and Notch2 inhibit myeloid differentiation in response to different cytokines.Mol Cell Biol. 1998;18:2324–2333.PubMedPubMedCentralGoogle Scholar
  175. 175.
    Schroeder T, Just U. Notch signalling via RBP-J promotes myeloid differentiation.EMBO J. 2000;19:2558–2568.PubMedPubMedCentralGoogle Scholar
  176. 176.
    Ohishi K, Varnum-Finney B, Serda RE, Anasetti C, Bernstein ID. The Notch ligand, Delta-1, inhibits the differentiation of mono-cytes into macrophages but permits their differentiation into dendritic cells.Blood. 2001;98:1402–1407.PubMedGoogle Scholar
  177. 177.
    Lam LT, Ronchini C, Norton J, Capobianco AJ, Bresnick EH. Suppression of erythroid but not megakaryocytic differentiation of human K562 erythroleukemic cells by notch-1.J Biol Chem. 2000;275:19676–19684.PubMedGoogle Scholar
  178. 178.
    Kumano K, Chiba S, Shimizu K, et al. Notch1 inhibits differentiation of hematopoietic cells by sustaining GATA-2 expression.Blood. 2001;98:3283–3289.PubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2002

Authors and Affiliations

  • K. Ohishi
    • 1
  • B. Varnum-Finney
    • 1
  • I. D. Bernstein
    • 1
    • 2
  1. 1.Clinical Research DivisionFred Hutchinson Cancer Research CenterSeattleUSA
  2. 2.Department of PediatricsThe University of WashingtonSeattleUSA

Personalised recommendations