Skip to main content
SpringerLink
Log in

The Molecular Basis of Notch Signaling: A Brief Overview

  • Chapter
Notch Signaling in Embryology and Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 727))

Abstract

The Notch signaling pathway is evolutionarily conserved and has been associated with numerous developmental processes, including stem cell maintenance and adult tissue homeostasis. Notably, both abnormal increases and deficiencies of Notch signaling result in human developmental anomalies and cancer development implying that the precise regulation of the intensity and duration of Notch signals is imperative. Numerous studies have demonstrated that the aberrant gain or loss of Notch signaling pathway components is critically linked to multiple human diseases. In this chapter, we will briefly summarize the molecular basis of Notch signaling, focusing on the modulation of Notch signals, and its developmental outcomes including vessel formation and the onset of cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Lai EC, Deblandre GA, Kintner C et al. Drosophila neuralized is a ubiquitin ligase that promotes the internalization and degradation of delta. Dev Cell 2001; 1(6):783–794.

    Article  PubMed  CAS  Google Scholar 

  2. Le Borgne R, Bardin A, Schweisguth F. The roles of receptor and ligand endocytosis in regulating Notch signalimg. Development 2005a; 132:1751–1762.

    Article  PubMed  Google Scholar 

  3. Bray SJ. Notch signaling: a simple pathway becomes complex. Nat Rev Mol Cell Biol 2006; 7:678–689.

    Article  PubMed  CAS  Google Scholar 

  4. Ehebauer M, Hayward P, Arias AM. Notch, a universal arbiter of cell fate decisions. Science 2006; 314: 1414–1415.

    Article  PubMed  CAS  Google Scholar 

  5. Ilagan MX, Kopan R. SnapShot: notch signaling pathway. Cell 2007; 128:1246.

    Article  PubMed  Google Scholar 

  6. Alva JA, Iruela-A rispe ML. Notch signaling in vascular morphogenesis. Curr Opin Hematol 2004; 11:278–283.

    Article  PubMed  CAS  Google Scholar 

  7. Hofmann JJ, Iruela-Arispe ML. Notch signaling in blood vessels: who is talking to whom about what? Circ Res 2007; 100:1556–1568.

    Article  PubMed  CAS  Google Scholar 

  8. Roca C, Adams RH. Regulation of vascular morphogenesis by Notch signaling. Genes Dev 2007; 21:2511–2524.

    Article  PubMed  CAS  Google Scholar 

  9. Phng LK, Gerhardt H. Angiogenesis: a team effort co-ordinated by notch. Dev Cell 2009; 16:196–208s.

    Article  PubMed  CAS  Google Scholar 

  10. Gridley. Notch signaling in vertebrate development and disease. Mol Cell Neurosci 1997; 9:103–108.

    Article  PubMed  CAS  Google Scholar 

  11. Garg V, Muth AN, Ransom JF et al. Mutation in NOTCH 1 cause aortic valve disease. Nature 2005; 21:180–184.

    Google Scholar 

  12. Grabher C, von Boehmer H, Look AT. Notch1 activation in the molecular pathogenesis of T-cell acute lymphoblastic leukaemia. Nat Rev Cancer 2006; 6(5):347–359.

    Article  PubMed  CAS  Google Scholar 

  13. Jundt F, Schwarzer R, Dörken B. Notch signaling in leukemias and lymphomas. Curr Mol Med 2008; 8:51–59.

    Article  PubMed  CAS  Google Scholar 

  14. Pancewicz J, Taylor JM, Datta A et al. Notch signaling contributes to proliferation and tumor formation of human T-cell leukemia virus type 1-associated adult T-cell leukemia. Proc Natl Acad Sci USA 2010; 107(38):16619–16624.

    Article  PubMed  CAS  Google Scholar 

  15. D’Souza B, Miyamoto A, Weinmaster G. The many facets of Notch ligands. Oncogene 2008; 27:5148–5167.

    Article  PubMed  Google Scholar 

  16. Brou C, Logeat F, Gupta N et al. A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metalloprotease TACE. Mol Cell 2000; 5:207–216.

    Article  PubMed  CAS  Google Scholar 

  17. De Strooper B, Annaert W, Cupers P et al. A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 1999; 398:518–522.

    Article  PubMed  Google Scholar 

  18. Okochi M, Steiner H, Fukumori A et al. Presenilins mediate a dual intramembranous gamma-secretase cleavage of Notch-1. EMBO J 2002; 21:5408–5416.

    Article  PubMed  CAS  Google Scholar 

  19. Wolfe MS, Kopan R. Intramembrane proteolysis: theme and variations. Science 2004; 305:1119–1123.

    Article  PubMed  CAS  Google Scholar 

  20. Selkoe DJ, Wolfe MS. Presenilin: running with scissors in the membrane. Cell 2007; 131:215–221.

    Article  PubMed  CAS  Google Scholar 

  21. Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science 1999; 284:770–776.

    Article  PubMed  CAS  Google Scholar 

  22. Petcherski AG, Kimble J. LAG-3 is a putative transcriptional activator in the C. elegans Notch pathway. Nature 2000; 405(6784):364–368.

    Article  PubMed  CAS  Google Scholar 

  23. Petcherski AG, Kimble J. Mastermind is a putative activator for Notch. Curr Biol 2000; 10(13):R471–R473.

    Article  PubMed  CAS  Google Scholar 

  24. F ryer CJ, White JB, Jones KA. Mastermind recruits CycC: CDK8 to phosphorylate the Notch ICD and co-ordinate activation with turnover. Mol Cell 2004; 16(4):509–520.

    Article  PubMed  CAS  Google Scholar 

  25. Wallberg AE, Pedersen K, Lendahl U et al. p300 and PCAF act co-operatively to mediate transcriptional activation from chromatin templates by notch intracellular domains in vitro. Mol Cell Biol 2002; 22(22):7812–7819.

    Article  PubMed  CAS  Google Scholar 

  26. Kovall RA. More complicated than it looks: assembly of Notch pathway transcription complexes. Oncogene 2008; 27:5099–5109.

    Article  PubMed  CAS  Google Scholar 

  27. Kopan R, Schroeter EH, Weintraub H et al. Signal transduction by activated mNotch: importance of proteolytic processing and its regulation by the extracellular domain. Proc Natl Acad Sci USA 1996; 93(4):1683–1688.

    Article  PubMed  CAS  Google Scholar 

  28. Buscarlet, Stifani S. The ‘Marx’ of Groucho on development and disease. Trends Cell Biol 2007; 17(7):353–361.

    Article  PubMed  CAS  Google Scholar 

  29. Le Borgne R. Regulation of Notch signalling by endocytosis and endosomal sorting. Curr Opin Cell Biol 2006; 18:213–222.

    Article  PubMed  Google Scholar 

  30. Nichols JT, Miyamoto A, Weinmaster G. Notch signaling—constantly on the move. Traffic 2007; 8(8):959–969.

    Article  PubMed  CAS  Google Scholar 

  31. Lai EC, Deblandre GA, Kintner C et al. Drosophila neuralized is a ubiquitin ligase that promotes the internalization and degradation of delta. Dev Cell 2001; 1(6):783–794.

    Article  PubMed  CAS  Google Scholar 

  32. Yeh E, Dermer M, Commisso C et al. Neuralized functions as an E3 ubiquitin ligase during Drosophila development. Curr Biol 2001; 11(21):1675–1679.

    Article  PubMed  CAS  Google Scholar 

  33. Panin VM, Papayannopoulos V, Wilson R et al. Fringe modulates Notch-ligand interactions. Nature 1997; 387(6636):908–912.

    Article  PubMed  CAS  Google Scholar 

  34. 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(3):283–288.

    Article  PubMed  CAS  Google Scholar 

  35. Johnston SH, Rauskolb C, Wilson R et al. A family of mammalian Fringe genes implicated in boundary determination and the Notch pathway. Development 1997; 124(11):2245–2254.

    PubMed  CAS  Google Scholar 

  36. Moloney DJ, Panin VM, Johnston SH et al. Fringe is a glycosyltransferase that modifies Notch. Nature 2000; 406(6794):369–375.

    Article  PubMed  CAS  Google Scholar 

  37. Acar M, Jafar-Nejad H, Takeuchi H et al. Rumi is a CAP10 domain glycosyltransferase that modifies Notch and is required for Notch signaling. Cell 2008; 132(2):247–258.

    Article  PubMed  CAS  Google Scholar 

  38. Hubbard EJ, Wu G, Kitajewski J, Greenwald I. sel-10, a negative regulator of lin-12 activity in Caenorhabditiselegans, encodes a member of the CDC4 family of proteins. Genes Dev 1997; 11(23):3182–9313.

    Article  PubMed  CAS  Google Scholar 

  39. Tsunematsu R, Nakayama K, Oike Y et al. Mouse Fbw7/Sel-10/Cdc4 is required for notch degradation during vascular development. J Biol Chem 2004; 279(10):9417–9423.

    Article  PubMed  CAS  Google Scholar 

  40. Gordon WR, Arnett KL, Blacklow SC. The molecular logic of Notch signaling—a structural and biochemical perspective. J Cell Sci 2008; 121:3109–3119.

    Article  PubMed  CAS  Google Scholar 

  41. Ju BG, Jeong S, Bae E et al. Fringe forms a complex with Notch. Nature 2000; 405(6783):191–195.

    Article  PubMed  CAS  Google Scholar 

  42. Brückner K, Perez L, Clausen H et al. Glycosyltransferase activity of Fringe modulates Notch-Delta interactions. Nature 2000; 406(6794):411–415.

    Article  PubMed  Google Scholar 

  43. Shimizu K, Chiba S, Kumano K et al. Mouse jagged1 physically interacts with Notch2 and other notch receptors. Assessment by quantitative methods. J Biol Chem 1999; 274(46):32961–3269.

    Article  PubMed  CAS  Google Scholar 

  44. Parks AL, Stout JR, Shepard SB et al. Structure-function analysis of delta trafficking, receptor binding and signaling in Drosophila. Genetics 2006; 174(4):1947–1961.

    Article  PubMed  CAS  Google Scholar 

  45. Carmeliet P, Ferreira V, Breier G et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 1996; 380(6573):435–439.

    Article  PubMed  CAS  Google Scholar 

  46. You LR, Lin FJ, Lee CT et al. Suppression of Notch signalling by the COUP-TFII transcription factor regulates vein identity. Nature 2005; 43:98–104.

    Article  Google Scholar 

  47. Iso T, Maeno T, Oike Y et al. Dll4-selective Notch signaling induces ephrinB2 gene expression in endothelialcells. Biochem Biophys Res Commun 2006; 341(3):708–714.

    Article  PubMed  CAS  Google Scholar 

  48. Domenga V, Fardoux P, Lacombe P et al. Notch3 is required for arterial identity and maturation of vascular smooth muscle cells. Genes Dev 2004; 18:2730–2735.

    Article  PubMed  CAS  Google Scholar 

  49. Krebs LT, Deftos ML, Bevan MJ et al. The Nrarp gene encodes an ankyrin-repeat protein that is transcriptionally regulated by the notch signaling pathway. Dev Biol 2001; 238:110–119.

    Article  PubMed  CAS  Google Scholar 

  50. Krebs LT, Shutter JR, Tanigaki K et al. Haploinsufficient lethality and formation of arteriovenous malformations in Notch pathway mutants. Genes Dev 2004; 18(20):2469–2473.

    Article  PubMed  CAS  Google Scholar 

  51. Gale NW, Dominguez MG, Noguera I et al. Haploinsufficiency of delta-like 4 ligand results in embryonic lethality due to major defects in arterial and vascular development. Proc Natl Acad Sci USA 2004; 10:15949–15954.

    Article  Google Scholar 

  52. 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.

    Article  PubMed  CAS  Google Scholar 

  53. Fischer A, Schumacher N, Maier M et al. The Notch target genes Hey1 and Hey2 are required for embryonic vascular development. Genes Dev 2004; 18:901–911.

    Article  PubMed  CAS  Google Scholar 

  54. Lawson ND, Scheer N, Pham VN et al. Notch signaling is required for arterial-venous differentiation during embryonic vascular development. Development 2001; 128(19):3675–3683.

    PubMed  CAS  Google Scholar 

  55. Zhong TP, Childs S, Leu JP et al. Gridlock signalling pathway fashions the first embryonic artery. Nature 2001; 414(6860):216–220.

    Article  PubMed  CAS  Google Scholar 

  56. Taylor KL, Henderson AM, Hughes CC. Notch activation during endothelial cell network formation in vitro targets the basic HLH transcription factor HESR-1 and downregulates VEGFR-2/KDR expression. Microvasc Res 2002; 64(3):372–383.

    Article  PubMed  CAS  Google Scholar 

  57. Kim YH, Hu H, Guevara-Gallardo S et al. Artery and veinsize is balanced by Notch and ephrin B2/EphB4 during angiogenesis. Development 2008; 135(22):3755–3764.

    Article  PubMed  CAS  Google Scholar 

  58. Hong CC, Peterson QP, Hong JY et al. Artery/vein specification is governed by opposing phosphatidylinositol-3 kinase and MAP kinase/ERK signaling. Curr Biol 2006; 16:1366–1372.

    Article  PubMed  CAS  Google Scholar 

  59. Holderfield MT, Henderson Anderson AM, Kokubo H et al. HESR1/CHF2 suppresses VEGFR2 transcription independent of binding to E-boxes. Biochem Biophys Res Commun 2006; 346(3):637–648.

    Article  PubMed  CAS  Google Scholar 

  60. Seo S, Fujita H, Nakano A et al. The forkhead transcription factors, Foxc1 and Foxc2, are required for arterial specification and lymphatic sprouting during vascular development. Dev Biol 2006; 294:458–470.

    Article  PubMed  CAS  Google Scholar 

  61. Hayashi H, Kume T. Foxc transcription factors directly regulate Dll4 and Hey2 expression by interacting with the VEGF-Notch signaling pathways in endothelial cells. PLoS ONE 2008; 3:e2401.

    Article  Google Scholar 

  62. Bentley K, Gerhardt H, Bates PA. Agent-based simulation of notch-mediated tip cell selection in angiogenic sprout initialisation. J Theor Biol 2008; 250:25–36.

    Article  PubMed  CAS  Google Scholar 

  63. Harrington LS, Sainson RC, Williams CK et al. Regulation of multiple angiogenic pathways by Dll4 and Notch in human umbilical vein endothelial cells. Microvasc Res 2008; 75:144–154.

    Article  PubMed  CAS  Google Scholar 

  64. Henderson AM, Wang SJ, Taylor AC et al. The basic helix-loop-helix transcription factor HESR1 regulates endothelial cell tube formation. J Biol Chem 2001; 276:6169–6176.

    Article  PubMed  CAS  Google Scholar 

  65. Holderfield MT, Henderson Anderson AM, Kokubo H et al. HESR1/CHF2 suppresses VEGFR2 transcription independent of binding to E-boxes. Biochem Biophys Res Commun 2006; 346(3):637–648.

    Article  Google Scholar 

  66. Shawber CJ, Funahashi Y, Francisco E et al. Notch alters VEGF responsiveness in human and murine endothelial cells by direct regulation of VEGFR-3 expression. J Clin Invest 2007; 117:3369–3382.

    Article  PubMed  CAS  Google Scholar 

  67. Sörensen I, Adams RH, Gossler A. DLL1-mediated Notch activation regulates endothelial identity in mouse fetal arteries. Blood 2009; 113(22):5680–5688.

    Article  PubMed  Google Scholar 

  68. Krebs LT, Xue Y, Norton CR et al. Notch signaling is essential for vascular morphogenesis in mice. Genes Dev 2000; 14:1343–1352.

    PubMed  CAS  Google Scholar 

  69. Pirot P, van Grunsven LA, Marine JC et al. Direct regulation of the Nrarp gene promoter by the Notch signaling pathway. Biochem Biophys Res Commun 2004; 322:526–534.

    Article  PubMed  CAS  Google Scholar 

  70. Masckauchán TN, Shawber CJ, Funahashi Y et al. Wnt/beta-catenin signaling induces proliferation, survival and interleukin-8 in human endothelial cells. Angiogenesis 2005; 8:43–51.

    Article  PubMed  Google Scholar 

  71. Ridgway J, Zhang G, Wu Y et al. Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis. Nature 2006; 444(7122):1083–1087.

    Article  PubMed  CAS  Google Scholar 

  72. Noguera-Troise I, Daly C, Papadopoulos NJ et al. Blockade of Dll4 inhibits tumour growth by promoting nonproductive angiogenesis. Nature 2006; 444:1032–1037.

    Article  PubMed  CAS  Google Scholar 

  73. Patel NS, Li JL, Generali D et al. Up-regulation of delta-like 4 ligand in human tumor vasculature and the role of basal expression in endothelial cell function. Cancer Res 2005; 65(19):8690–8697.

    Article  PubMed  CAS  Google Scholar 

  74. Patel NS, Dobbie MS, Rochester M et al. Up-regulation of endothelial delta-like 4 expression correlates with vessel maturation in bladder cancer. Clin Cancer Res 2006; 12(16):4836–4844.

    Article  PubMed  CAS  Google Scholar 

  75. Scehnet JS, Jiang W, Kumar SR et al. Inhibition of Dll4-mediated signaling induces proliferation of immature vessels and results in poor tissue perfusion. Blood 2007; 109(11):4753–4760.

    Article  PubMed  CAS  Google Scholar 

  76. Noguera-Troise I, Daly C, Papadopoulos NJ et al. Blockade of Dll4 inhibits tumour growth by promoting nonproductive angiogenesis. Nature 2006; 444(7122):1032–1037.

    Article  PubMed  CAS  Google Scholar 

  77. Ridgway J, Zhang G, Wu Y et al. Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis. Nature 2006; 444:1083–1087.

    Article  PubMed  CAS  Google Scholar 

  78. Gallahan D, Callahan R. Mammary tumorigenesis in feral mice: identification of a new int locus in mouse mammary tumor virus (Czech II)-induced mammary tumors. J Virol 1987; 61(1):66–74.

    PubMed  CAS  Google Scholar 

  79. Diévart A, Beaulieu N, Jolicoeur P. Involvement of Notch1 in the development of mouse mammary tumors. Oncogene 1999; 18(44):5973–5981.

    Article  PubMed  Google Scholar 

  80. Parr C, Watkins G, Jiang WG. The possible correlation of Notch-1 and Notch-2 with clinical outcome and tumour clinic opathological parameters in human breast cancer. Int J Mol Med 2004; 14(5):779–786.

    PubMed  CAS  Google Scholar 

  81. Weijzen S, Rizzo P, Braid M et al. Activation of Notch-1 signaling maintains the neoplastic phenotype in human Ras-transformed cells. Nat Med 2002; 8(9):979–986.

    Article  PubMed  CAS  Google Scholar 

  82. Parkin DM. Cancer in developing countries. Cancer Surveys 1994; 19–20:519–561.

    PubMed  Google Scholar 

  83. Goodlad RA, Ryan AJ, Wedge SR et al. Inhibiting vascular endothelial growth factor receptor-2 signaling reduces tumor burden in the ApcMin/??mouse model of early intestinal cancer. Carcinogenesis 2006; 27(10):2133–2139.

    Article  PubMed  CAS  Google Scholar 

  84. Korsisaari N, Kasman IM, Forrest WF et al. Inhibition of VEGF-A prevents the angiogenic switch and results in increased survival of Apc?/min mice. Proc Natl Acad Sci USA 2007; 104(25):10625–10630.

    Article  PubMed  CAS  Google Scholar 

  85. Ferrara N, Clapp C, Weiner R. The 16K fragment of prolactin specifically inhibits basal or fibroblast growth factor stimulated growth of capillary endothelial cells. Endocrinology 1991; 129(2):896–900.

    Article  PubMed  CAS  Google Scholar 

  86. Thurston G, Noguera-Troise I, Yancopoulos GD. The Delta paradox: DLL4 blockade leads to more tumour vessels but less tumour growth. Nat Rev Cancer 2007; 7(5):327–331.

    Article  PubMed  CAS  Google Scholar 

  87. Indraccolo S, Minuzzo S, Masiero M et al. Cross-talk between tumor and endothelial cells involving the Notch3-Dll4 interaction marks escape from tumor dormancy. Cancer Res 2009; 69(4):1314–1323.

    Article  PubMed  CAS  Google Scholar 

  88. Liu ZJ, Xiao M, Balint K et al. Notchl signaling promotes primary melanoma progression by activating mitogen-activated protein kinase/phosphatidylinositol 3-kinase-Akt pathways and up-regulating N-cadherin expression. Cancer Res 2006; 66(8):4182–4190.

    Article  PubMed  CAS  Google Scholar 

  89. Patel NS, Li JL, Generali D et al. Up-regulation of delta-like 4 ligand in human tumor vasculature and the role of basal expression in endothelial cell function. Cancer Res 2005; 65:8690–8697.

    Article  PubMed  CAS  Google Scholar 

  90. Jubb AM, Turley H, Moeller HC et al. Expression of delta-like ligand 4 (Dll4) and markers of hypoxia in colon cancer. Br J Cancer 2009; 101(10):1749–1757.

    Article  PubMed  CAS  Google Scholar 

  91. Good K, Ciosk R, Nance J et al. The T-box transcription factors TBX-37 and TBX-38 link GLP-1/Notch signaling to mesoderm induction in C. elegans embryos. Development 2004; 131(9):1967–1978.

    Article  PubMed  CAS  Google Scholar 

  92. Oka C, Nakano T, Wakeham A et al. Disruption of the mouse RBP-J kappa gene results in early embryonic death. Development 1995; 121(10):3291–3301.

    PubMed  CAS  Google Scholar 

  93. Donoviel DB, Hadjantonakis AK, Ikeda M et al. Mice lacking both presenilin genes exhibit early embryonic patterning defects. Genes Dev 1999; 13(21):2801–2810.

    Article  PubMed  CAS  Google Scholar 

  94. Shi S, Stanley P. Protein O-fucosyltransferase 1 is an essential component of Notch signaling pathways. Proc Natl Acad Sci USA 2003; 100(9):5234–5239.

    Article  PubMed  CAS  Google Scholar 

  95. Timmerman LA, Grego-Bessa J, Raya A et al. Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Genes Dev 2004; 18(1):99–115.

    Article  PubMed  CAS  Google Scholar 

  96. Grego-Bessa J, Díez J, Timmerman L et al. Notch and epithelial-mesenchyme transition in development and tumor progression: another turn of the screw. Cell Cycle 2004; 3(6):718–721.

    Article  PubMed  CAS  Google Scholar 

  97. Corbo JC, Fujiwara S, Levine M et al. Suppressor of hairless activates brachyury expression in the Ciona embryo. Dev Biol 1998; 203(2):358–368.

    Article  PubMed  CAS  Google Scholar 

  98. Corbo JC, Levine M, Zeller RW. Characterization of a notochord-specific enhancer from the Brachyury promoter region of the ascidian, Cionaintestinalis. Development 1997; 124(3):589–602.

    PubMed  CAS  Google Scholar 

  99. Tapanes-Castillo A, Baylies MK. Notch signaling patterns Drosophila mesodermal segments by regulating the bHLH transcription factor twist. Development 2004; 131(10):2359–2372.

    Article  PubMed  CAS  Google Scholar 

  100. Kikuchi Y, Verkade H, Reiter JF et al. Notch signaling can regulate endoderm formation in zebrafish. Dev Dyn 2004; 229(4):756–762.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, School of Medicine, Pusan National University, Pusan, Korea

    Sang-Mo Kwon & Sang-Hun Lee

  2. Department of Regenerative Medicine, School of Medicine, Tokai University, Kanagawa, Japan

    Takayuki Asahara

  3. Vascular Regeneration Research Group, Institute of Biomedical Research and Innovation, Kobe, Japan

    Cantas Alev & Takayuki Asahara

  4. Laboratory for Early Embryogenesis, RIKEN Center for Developmental Biology, Kobe, Japan

    Cantas Alev

Authors
  1. Sang-Mo Kwon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cantas Alev
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sang-Hun Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takayuki Asahara
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Takayuki Asahara .

Editor information

Editors and Affiliations

  1. Department of Dermatology, The Saarland University Hospital, Homburg, Germany

    Jörg Reichrath

  2. Department of Internal Medicine I, The Saarland University Hospital, Homburg, Germany

    Sandra Reichrath

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Landes Bioscience and Springer Science+Business Media

About this chapter

Cite this chapter

Kwon, SM., Alev, C., Lee, SH., Asahara, T. (2012). The Molecular Basis of Notch Signaling: A Brief Overview. In: Reichrath, J., Reichrath, S. (eds) Notch Signaling in Embryology and Cancer. Advances in Experimental Medicine and Biology, vol 727. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0899-4_1

Download citation

Publish with us

Policies and ethics

Search

Navigation