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Fibronectins Are Essential for Heart and Blood Vessel Morphogenesis But Are Dispensable for Initial Specification of Precursor Cells
Elizabeth L. George,
H. Scott Baldwin, and
Richard O. Hynes
From the Vascular Research Division, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Division of Pediatric Cardiology, Children's Hospital of Philadelphia, Philadelphia, PA; and Howard Hughes Medical Institute, Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA.
The underlying mechanisms of lethal cardiovascular defects associated with the fibronectin-null (FN.null) mutation in mouse embryos were investigated by lineage analysis of myocardial, endocardial, and endothelial cells. A wide variation in phenotype was observed on two genetic backgrounds. In the less severe class (C57/BL6 background), FN.null embryos display a defective heart. Myocardial cells express the specific marker MF-20 and are correctly localized in the anterior trunk region, but myocardial organization is disrupted, resulting in a bulbous heart tube. Endocardial cells express the specific marker platelet-endothelial cell adhesion molecule-1 (PECAM-1) and are localized within the myocardium, but the endocardium appears collapsed. Endothelial cells of two vascular beds are specified, but the aortae are distended and lack contact with the surrounding mesenchyme, while no vessels form in the yolk sac. Defects in the more severe class suggest that FNs are essential earlier in development on the 129/Sv background. Myocardial and endocardial cells are specified, but morphogenesis of the myocardium and endocardium does not occur. Aortic endothelial cells are specified and localized normally, but remain scattered. Yolk sac endothelial cells resemble those of the less severe class. We conclude that FNs are essential for organization of heart and blood vessels, but are dispensable for cellular specification in the appropriate regions within the embryo.
Blood, Vol. 90 No. 8 (July 15), 1997:
pp. 3073-3081
© 1997 by The American Society of Hematology.
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Arginyltransferase regulates alpha cardiac actin function, myofibril formation and contractility during heart development
Development,
December 1, 2008;
135(23):
3881 - 3889.
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Platelet-Derived Growth Factor Receptors Direct Vascular Development Independent of Vascular Smooth Muscle Cell Function
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28(18):
5646 - 5657.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Kinsey, M. R. Williamson, S. Chaudhry, K. T. Mellody, A. McGovern, S. Takahashi, C. A. Shuttleworth, and C. M. Kielty
Fibrillin-1 microfibril deposition is dependent on fibronectin assembly
J. Cell Sci.,
August 15, 2008;
121(16):
2696 - 2704.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. J. Sundberg-Smith, L. A. DiMichele, R. L. Sayers, C. P. Mack, and J. M. Taylor
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102(12):
1502 - 1511.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. R. Carlson, H. Hu, R. Braren, Y. H. Kim, and R. A. Wang
Cell-autonomous requirement for {beta}1 integrin in endothelial cell adhesion, migration and survival during angiogenesis in mice
Development,
June 15, 2008;
135(12):
2193 - 2202.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Jakobsson, A. Domogatskaya, K. Tryggvason, D. Edgar, and L. Claesson-Welsh
Laminin deposition is dispensable for vasculogenesis but regulates blood vessel diameter independent of flow
FASEB J,
May 1, 2008;
22(5):
1530 - 1539.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Abraham, N. Kogata, R. Fassler, and R. H. Adams
Integrin {beta}1 Subunit Controls Mural Cell Adhesion, Spreading, and Blood Vessel Wall Stability
Circ. Res.,
March 14, 2008;
102(5):
562 - 570.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. C. Feral, A. Zijlstra, E. Tkachenko, G. Prager, M. L. Gardel, M. Slepak, and M. H. Ginsberg
CD98hc (SLC3A2) participates in fibronectin matrix assembly by mediating integrin signaling
J. Cell Biol.,
August 9, 2007;
178(4):
701 - 711.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Schmidt, K. Brixius, and W. Bloch
Endothelial Precursor Cell Migration During Vasculogenesis
Circ. Res.,
July 20, 2007;
101(2):
125 - 136.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. L. Boyd, S. K. Dhara, R. Rekaya, E. A. Godbey, K. Hasneen, R. R. Rao, F. D. West III, B. A. Gerwe, and S. L. Stice
BMP4 Promotes Formation of Primitive Vascular Networks in Human Embryonic Stem Cell-Derived Embryoid Bodies
Experimental Biology and Medicine,
June 1, 2007;
232(6):
833 - 843.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Sandal, K. Valyi-Nagy, V. A. Spencer, R. Folberg, M. J. Bissell, and A. J. Maniotis
Epigenetic Reversion of Breast Carcinoma Phenotype Is Accompanied by Changes in DNA Sequestration as Measured by AluI Restriction Enzyme
Am. J. Pathol.,
May 1, 2007;
170(5):
1739 - 1749.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. S. Wijelath, S. Rahman, M. Namekata, J. Murray, T. Nishimura, Z. Mostafavi-Pour, Y. Patel, Y. Suda, M. J. Humphries, and M. Sobel
Heparin-II Domain of Fibronectin Is a Vascular Endothelial Growth Factor-Binding Domain: Enhancement of VEGF Biological Activity by a Singular Growth Factor/Matrix Protein Synergism
Circ. Res.,
October 13, 2006;
99(8):
853 - 860.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Tang, F. Mack, V. H. Haase, M. C. Simon, and R. S. Johnson
pVHL Function Is Essential for Endothelial Extracellular Matrix Deposition.
Mol. Cell. Biol.,
April 1, 2006;
26(7):
2519 - 2530.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Mitola, B. Brenchio, M. Piccinini, L. Tertoolen, L. Zammataro, G. Breier, M. T. Rinaudo, J. den Hertog, M. Arese, and F. Bussolino
Type I Collagen Limits VEGFR-2 Signaling by a SHP2 Protein-Tyrosine Phosphatase-Dependent Mechanism 1
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98(1):
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[Abstract]
[Full Text]
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|
|
|
|
|
|
|
E. M. Morin-Kensicki, B. N. Boone, M. Howell, J. R. Stonebraker, J. Teed, J. G. Alb, T. R. Magnuson, W. O'Neal, and S. L. Milgram
Defects in Yolk Sac Vasculogenesis, Chorioallantoic Fusion, and Embryonic Axis Elongation in Mice with Targeted Disruption of Yap65
Mol. Cell. Biol.,
January 1, 2006;
26(1):
77 - 87.
[Abstract]
[Full Text]
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|
|
|
|
|
|
|
S. Astrof, D. Crowley, E. L. George, T. Fukuda, K. Sekiguchi, D. Hanahan, and R. O. Hynes
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Mol. Cell. Biol.,
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24(19):
8662 - 8670.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Vokes, T. A. Yatskievych, R. L. Heimark, J. McMahon, A. P. McMahon, P. B. Antin, and P. A. Krieg
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September 1, 2004;
131(17):
4371 - 4380.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. H. Tan, Z. Sun, S. L. Opitz, T. E. Schmidt, J. H. Peters, and E. L. George
Deletion of the alternatively spliced fibronectin EIIIA domain in mice reduces atherosclerosis
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July 1, 2004;
104(1):
11 - 18.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. L. Bohnsack, L. Lai, P. Dolle, and K. K. Hirschi
Signaling hierarchy downstream of retinoic acid that independently regulates vascular remodeling and endothelial cell proliferation
Genes & Dev.,
June 1, 2004;
18(11):
1345 - 1358.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. J. Sundberg, L. M. Galante, H. M. Bill, C. P. Mack, and J. M. Taylor
An Endogenous Inhibitor of Focal Adhesion Kinase Blocks Rac1/JNK but Not Ras/ERK-dependent Signaling in Vascular Smooth Muscle Cells
J. Biol. Chem.,
August 8, 2003;
278(32):
29783 - 29791.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. C. Wendler, A. Schmoldt, G. R. Flentke, L. C. Case, L. Quadro, W. S. Blaner, J. Lough, and S. M. Smith
Increased Fibronectin Deposition in Embryonic Hearts of Retinol-Binding Protein-Null Mice
Circ. Res.,
May 2, 2003;
92(8):
920 - 928.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Ilic, B. Kovacic, S. McDonagh, F. Jin, C. Baumbusch, D. G. Gardner, and C. H. Damsky
Focal Adhesion Kinase Is Required for Blood Vessel Morphogenesis
Circ. Res.,
February 21, 2003;
92(3):
300 - 307.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. L. Brutsaert
Cardiac Endothelial-Myocardial Signaling: Its Role in Cardiac Growth, Contractile Performance, and Rhythmicity
Physiol Rev,
January 1, 2003;
83(1):
59 - 115.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Sottile and D. C. Hocking
Fibronectin Polymerization Regulates the Composition and Stability of Extracellular Matrix Fibrils and Cell-Matrix Adhesions
Mol. Biol. Cell,
October 1, 2002;
13(10):
3546 - 3559.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. S. Wijelath, J. Murray, S. Rahman, Y. Patel, A. Ishida, K. Strand, S. Aziz, C. Cardona, W. P. Hammond, G. F. Savidge, et al.
Novel Vascular Endothelial Growth Factor Binding Domains of Fibronectin Enhance Vascular Endothelial Growth Factor Biological Activity
Circ. Res.,
July 12, 2002;
91(1):
25 - 31.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Gu, S. Muller, V. Mancino, S. Offermanns, and M. I. Simon
Interaction of Galpha 12 with Galpha 13 and Galpha q signaling pathways
PNAS,
July 9, 2002;
99(14):
9352 - 9357.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. E. Francis, K. L. Goh, K. Hodivala-Dilke, B. L. Bader, M. Stark, D. Davidson, and R. O. Hynes
Central Roles of {alpha}5{beta}1 Integrin and Fibronectin in Vascular Development in Mouse Embryos and Embryoid Bodies
Arterioscler Thromb Vasc Biol,
June 1, 2002;
22(6):
927 - 933.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R.O. HYNES, J.C. LIVELY, J.H. MCCARTY, D. TAVERNA, S.E. FRANCIS, K. HODIVALA-DILKE, and Q. XIAO
The Diverse Roles of Integrins and Their Ligands in Angiogenesis
Cold Spring Harb Symp Quant Biol,
January 1, 2002;
67(0):
143 - 154.
[Abstract]
[PDF]
|
|
|
|
|
|
|
G. Kostka, R. Giltay, W. Bloch, K. Addicks, R. Timpl, R. Fassler, and M.-L. Chu
Perinatal Lethality and Endothelial Cell Abnormalities in Several Vessel Compartments of Fibulin-1-Deficient Mice
Mol. Cell. Biol.,
October 15, 2001;
21(20):
7025 - 7034.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Charron, G. Tsimiklis, M. Arcand, L. Robitaille, Q. Liang, J. D. Molkentin, S. Meloche, and M. Nemer
Tissue-specific GATA factors are transcriptional effectors of the small GTPase RhoA
Genes & Dev.,
October 15, 2001;
15(20):
2702 - 2719.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Bouvard, C. Brakebusch, E. Gustafsson, A. Aszodi, T. Bengtsson, A. Berna, and R. Fassler
Functional Consequences of Integrin Gene Mutations in Mice
Circ. Res.,
July 30, 2001;
89(3):
211 - 223.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. KERNEC, M. UNLU, W. LABEIKOVSKY, J. S. MINDEN, and A. P. KORETSKY
Changes in the mitochondrial proteome from mouse hearts deficient in creatine kinase
Physiol Genomics,
July 17, 2001;
6(2):
117 - 128.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. S. Ross and T. K. Borg
Integrins and the Myocardium
Circ. Res.,
June 8, 2001;
88(11):
1112 - 1119.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. S. Keller, S.-Y. Shai, C. J. Babbitt, C. G. Pham, R. J. Solaro, M. L. Valencik, J. C. Loftus, and R. S. Ross
Disruption of Integrin Function in the Murine Myocardium Leads to Perinatal Lethality, Fibrosis, and Abnormal Cardiac Performance
Am. J. Pathol.,
March 1, 2001;
158(3):
1079 - 1090.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. L. Valencik and J. A. McDonald
Cardiac expression of a gain-of-function {alpha}5-integrin results in perinatal lethality
Am J Physiol Heart Circ Physiol,
January 1, 2001;
280(1):
H361 - H367.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. M. Adelman, M. Gertsenstein, A. Nagy, M. C. Simon, and E. Maltepe
Placental cell fates are regulated in vivo by HIF-mediated hypoxia responses
Genes & Dev.,
December 15, 2000;
14(24):
3191 - 3203.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
C. G. Pham, A. E. Harpf, R. S. Keller, H. T. Vu, S.-Y. Shai, J. C. Loftus, and R. S. Ross
Striated muscle-specific beta 1D-integrin and FAK are involved in cardiac myocyte hypertrophic response pathway
Am J Physiol Heart Circ Physiol,
December 1, 2000;
279(6):
H2916 - H2926.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Cirulli, G. M. Beattie, G. Klier, M. Ellisman, C. Ricordi, V. Quaranta, F. Frasier, J. K. Ishii, A. Hayek, and D. R. Salomon
Expression and Function of {alpha}v{beta}3 and {alpha}v{beta}5 Integrins in the Developing Pancreas: Roles in the Adhesion and Migration of Putative Endocrine Progenitor Cells
J. Cell Biol.,
September 18, 2000;
150(6):
1445 - 1460.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Huo, A. Hafezi-Moghadam, and K. Ley
Role of Vascular Cell Adhesion Molecule-1 and Fibronectin Connecting Segment-1 in Monocyte Rolling and Adhesion on Early Atherosclerotic Lesions
Circ. Res.,
July 21, 2000;
87(2):
153 - 159.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. F. Muro, M. L. Marro, S. Gajovic, F. Porro, L. Luzzatto, and F. E. Baralle
Mild spherocytic hereditary elliptocytosis and altered levels of alpha - and gamma -adducins in beta -adducin-deficient mice
Blood,
June 15, 2000;
95(12):
3978 - 3985.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Oliviero, C. Chassagne, N. Salichon, A. Corbier, G. Hamon, F. Marotte, D. Charlemagne, L. Rappaport, and J.-L. Samuel
Expression of laminin {alpha}2 chain during normal and pathological growth of myocardium in rat and human
Cardiovasc Res,
May 1, 2000;
46(2):
346 - 355.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. F. Brown, A. J. Guidi, S. J. Schnitt, L. Van De Water, M. L. Iruela-Arispe, T.-K. Yeo, K. Tognazzi, and H. F. Dvorak
Vascular Stroma Formation in Carcinoma in Situ, Invasive Carcinoma, and Metastatic Carcinoma of the Breast
Clin. Cancer Res.,
May 1, 1999;
5(5):
1041 - 1056.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M Tanaka, Z Chen, S Bartunkova, N Yamasaki, and S Izumo
The cardiac homeobox gene Csx/Nkx2.5 lies genetically upstream of multiple genes essential for heart development
Development,
January 3, 1999;
126(6):
1269 - 1280.
[Abstract]
[PDF]
|
|
|
|
|
