Human Molecular Genetics, Vol 8, 723-730, Copyright © 1999 by Oxford University Press
Y Xue, X Gao, CE Lindsell, CR Norton, B Chang, C Hicks, M Gendron-Maguire, EB Rand, G Weinmaster and T Gridley
The Notch signaling pathway is an evolutionarily conserved intercellular
signaling mechanism essential for embryonic development in mammals.
Mutations in the human JAGGED1 ( JAG1 ) gene, which encodes a ligand for
the Notch family of transmembrane receptors, cause the autosomal dominant
disorder Alagille syndrome. We have examined the in vivo role of the mouse
Jag1 gene by creating a null allele through gene targeting. Mice homozygous
for the Jag1 mutation die from hemorrhage early during embryogenesis,
exhibiting defects in remodeling of the embryonic and yolk sac vasculature.
We mapped the Jag1 gene to mouse chromosome 2, in the vicinity of the
Coloboma ( Cm ) deletion. Molecular and complementation analyses revealed
that the Jag1 gene is functionally deleted in the Cm mutant allele. Mice
heterozygous for the Jag1 null allele exhibit an eye dysmorphology similar
to that of Cm /+ heterozygotes, but do not exhibit other phenotypes
characteristic of Cm /+ mice or of humans with Alagille syndrome. These
results establish the phenotype of Cm /+ mice as a contiguous gene deletion
syndrome and demonstrate that Jag1 is essential for remodeling of the
embryonic vasculature.
ARTICLES
Embryonic lethality and vascular defects in mice lacking the Notch ligand Jagged1
The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609-1500, USA.
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A. Proweller, W. S. Pear, and M. S. Parmacek Notch Signaling Represses Myocardin-induced Smooth Muscle Cell Differentiation J. Biol. Chem., March 11, 2005; 280(10): 8994 - 9004. [Abstract] [Full Text] [PDF]
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S. M. Vercauteren and H. J. Sutherland Constitutively active Notch4 promotes early human hematopoietic progenitor cell maintenance while inhibiting differentiation and causes lymphoid abnormalities in vivo Blood, October 15, 2004; 104(8): 2315 - 2322. [Abstract] [Full Text] [PDF]
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H. Kokubo, S. Miyagawa-Tomita, H. Tomimatsu, Y. Nakashima, M. Nakazawa, Y. Saga, and R. L. Johnson Targeted Disruption of hesr2 Results in Atrioventricular Valve Anomalies That Lead to Heart Dysfunction Circ. Res., September 3, 2004; 95(5): 540 - 547. [Abstract] [Full Text] [PDF]
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S. Shi and P. Stanley Protein O-fucosyltransferase 1 is an essential component of Notch signaling pathways PNAS, April 29, 2003; 100(9): 5234 - 5239. [Abstract] [Full Text] [PDF]
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D. Small, D. Kovalenko, R. Soldi, A. Mandinova, V. Kolev, R. Trifonova, C. Bagala, D. Kacer, C. Battelli, L. Liaw, et al. Notch Activation Suppresses Fibroblast Growth Factor-dependent Cellular Transformation J. Biol. Chem., April 25, 2003; 278(18): 16405 - 16413. [Abstract] [Full Text] [PDF]
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A. Slavotinek and L. G. Biesecker Genetic modifiers in human development and malformation syndromes, including chaperone proteins Hum. Mol. Genet., April 2, 2003; 12(90001): R45 - 50. [Abstract] [Full Text] [PDF]
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T. Schroeder, S. T. Fraser, M. Ogawa, S. Nishikawa, C. Oka, G. W. Bornkamm, S.-I. Nishikawa, T. Honjo, and U. Just Recombination signal sequence-binding protein Jkappa alters mesodermal cell fate decisions by suppressing cardiomyogenesis PNAS, April 1, 2003; 100(7): 4018 - 4023. [Abstract] [Full Text] [PDF]
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B. McCright, J. Lozier, and T. Gridley A mouse model of Alagille syndrome: Notch2 as a genetic modifier of Jag1 haploinsufficiency Development, March 4, 2003; 129(4): 1075 - 1082. [Abstract] [Full Text] [PDF]
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T. Takahashi, K. Takahashi, P. L. St. John, P. A. Fleming, T. Tomemori, T. Watanabe, D. R. Abrahamson, C. J. Drake, T. Shirasawa, and T. O. Daniel A Mutant Receptor Tyrosine Phosphatase, CD148, Causes Defects in Vascular Development Mol. Cell. Biol., March 1, 2003; 23(5): 1817 - 1831. [Abstract] [Full Text] [PDF]
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Z.-J. Liu, T. Shirakawa, Y. Li, A. Soma, M. Oka, G. P. Dotto, R. M. Fairman, O. C. Velazquez, and M. Herlyn Regulation of Notch1 and Dll4 by Vascular Endothelial Growth Factor in Arterial Endothelial Cells: Implications for Modulating Arteriogenesis and Angiogenesis Mol. Cell. Biol., January 1, 2003; 23(1): 14 - 25. [Abstract] [Full Text]
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 J. Morrissey, G. Guo, K. Moridaira, M. Fitzgerald, R. McCracken, T. Tolley, and S. Klahr Transforming Growth Factor-{beta} Induces Renal Epithelial Jagged-1 Expression in Fibrotic Disease J. Am. Soc. Nephrol., June 1, 2002; 13(6): 1499 - 1508. [Abstract] [Full Text] [PDF]
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S. S. Nijjar, L. Wallace, H. A. Crosby, S. G. Hubscher, and A. J. Strain Altered Notch Ligand Expression in Human Liver Disease : Further Evidence for a Role of the Notch Signaling Pathway in Hepatic Neovascularization and Biliary Ductular Defects Am. J. Pathol., May 1, 2002; 160(5): 1695 - 1703. [Abstract] [Full Text] [PDF]
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K. G. Leong, X. Hu, L. Li, M. Noseda, B. Larrivee, C. Hull, L. Hood, F. Wong, and A. Karsan Activated Notch4 Inhibits Angiogenesis: Role of {beta}1-Integrin Activation Mol. Cell. Biol., April 15, 2002; 22(8): 2830 - 2841. [Abstract] [Full Text] [PDF]
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S. L. Dunwoodie, M. Clements, D. B. Sparrow, X. Sa, R. A. Conlon, and R. S. P. Beddington Axial skeletal defects caused by mutation in the spondylocostal dysplasia/pudgy gene Dll3 are associated with disruption of the segmentation clock within the presomitic mesoderm Development, January 4, 2002; 129(7): 1795 - 1806. [Abstract] [Full Text] [PDF]
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 B.M. WEINSTEIN and N.D. LAWSON Arteries, Veins, Notch, and VEGF Cold Spring Harb Symp Quant Biol, January 1, 2002; 67(0): 155 - 162. [Abstract] [PDF]
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N. D. Lawson, N. Scheer, V. N. Pham, C.-H. Kim, A. B. Chitnis, J. A. Campos-Ortega, and B. M. Weinstein Notch signaling is required for arterial-venous differentiation during embryonic vascular development Development, October 1, 2001; 128(19): 3675 - 3683. [Abstract] [Full Text] [PDF]
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V. Lindner, C. Booth, I. Prudovsky, D. Small, T. Maciag, and L. Liaw Members of the Jagged/Notch Gene Families Are Expressed in Injured Arteries and Regulate Cell Phenotype via Alterations in Cell Matrix and Cell-Cell Interaction Am. J. Pathol., September 1, 2001; 159(3): 875 - 883. [Abstract] [Full Text] [PDF]
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T. Gridley Notch signaling during vascular development PNAS, May 8, 2001; 98(10): 5377 - 5378. [Full Text] [PDF]
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H. Uyttendaele, J. Ho, J. Rossant, and J. Kitajewski Vascular patterning defects associated with expression of activated Notch4 in embryonic endothelium PNAS, May 8, 2001; 98(10): 5643 - 5648. [Abstract] [Full Text] [PDF]
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A. E. Kiernan, N. Ahituv, H. Fuchs, R. Balling, K. B. Avraham, K. P. Steel, and M. H. de Angelis The Notch ligand Jagged1 is required for inner ear sensory development PNAS, March 16, 2001; (2001) 71496998. [Abstract] [Full Text]
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H. Tsai, R. E. Hardisty, C. Rhodes, A. E. Kiernan, P. Roby, Z. Tymowska-Lalanne, P. Mburu, S. Rastan, A. J. Hunter, S. D. M. Brown, et al. The mouse slalom mutant demonstrates a role for Jagged1 in neuroepithelial patterning in the organ of Corti Hum. Mol. Genet., March 1, 2001; 10(5): 507 - 512. [Abstract] [Full Text] [PDF]
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 E. M. Conway, D. Collen, and P. Carmeliet Molecular mechanisms of blood vessel growth Cardiovasc Res, February 16, 2001; 49(3): 507 - 521. [Full Text] [PDF]
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B McCright, X Gao, L Shen, J Lozier, Y Lan, M Maguire, D Herzlinger, G Weinmaster, R Jiang, and T Gridley Defects in development of the kidney, heart and eye vasculature in mice homozygous for a hypomorphic Notch2 mutation Development, January 2, 2001; 128(4): 491 - 502. [Abstract] [PDF]
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Z. A. Eldadah, A. Hamosh, N. J. Biery, R. A. Montgomery, M. Duke, R. Elkins, and H. C. Dietz Familial Tetralogy of Fallot caused by mutation in the jagged1 gene Hum. Mol. Genet., January 1, 2001; 10(2): 163 - 169. [Abstract] [Full Text] [PDF]
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 M. Mina Regulation of Mandibular Growth and Morphogenesis Critical Reviews in Oral Biology & Medicine, January 1, 2001; 12(4): 276 - 300. [Abstract] [Full Text] [PDF]
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K. Shimizu, S. Chiba, N. Hosoya, K. Kumano, T. Saito, M. Kurokawa, Y. Kanda, Y. Hamada, and H. Hirai Binding of Delta1, Jagged1, and Jagged2 to Notch2 Rapidly Induces Cleavage, Nuclear Translocation, and Hyperphosphorylation of Notch2 Mol. Cell. Biol., September 15, 2000; 20(18): 6913 - 6922. [Abstract] [Full Text]
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D. A Cabezas, R. Slaugh, F. Abidi, J F. Arena, R. E Stevenson, C. E Schwartz, and H. A Lubs A new X linked mental retardation (XLMR) syndrome with short stature, small testes, muscle wasting, and tremor localises to Xq24-q25. J. Med. Genet., September 1, 2000; 37(9): 663 - 668. [Abstract] [Full Text]
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L. T. Krebs, Y. Xue, C. R. Norton, J. R. Shutter, M. Maguire, J. P. Sundberg, D. Gallahan, V. Closson, J. Kitajewski, R. Callahan, et al. Notch signaling is essential for vascular morphogenesis in mice Genes & Dev., June 1, 2000; 14(11): 1343 - 1352. [Abstract] [Full Text]
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 G. F. Hoyne, I. Le Roux, M. Corsin-Jimenez, K. Tan, J. Dunne, L. M. G. Forsyth, M. J. Dallman, M. J. Owen, D. Ish-Horowicz, and J. R. Lamb Serrate1-induced Notch signalling regulates the decision between immunity and tolerance made by peripheral CD4+ T cells Int. Immunol., February 1, 2000; 12(2): 177 - 185. [Abstract] [Full Text] [PDF]
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T. Maynard, Y Wakamatsu, and J. Weston Cell interactions within nascent neural crest cell populations transiently promote death of neurogenic precursors Development, January 11, 2000; 127(21): 4561 - 4572. [Abstract] [PDF]
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A Zine, T. Van De Water, and F de Ribaupierre Notch signaling regulates the pattern of auditory hair cell differentiation in mammals Development, January 8, 2000; 127(15): 3373 - 3383. [Abstract] [PDF]
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A. Parks, K. Klueg, J. Stout, and M. Muskavitch Ligand endocytosis drives receptor dissociation and activation in the Notch pathway Development, January 4, 2000; 127(7): 1373 - 1385. [Abstract] [PDF]
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L. T. Lam, C. Ronchini, J. Norton, A. J. Capobianco, and E. H. Bresnick Suppression of Erythroid but Not Megakaryocytic Differentiation of Human K562 Erythroleukemic Cells by Notch-1 J. Biol. Chem., June 23, 2000; 275(26): 19676 - 19684. [Abstract] [Full Text] [PDF]
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