spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search    

The fully linked HTML version of this article has now been published.
Development ePress online publication date 2 Dec 2004
doi: 10.1242/dev.01551

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dev.01551v1
132/1/165    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by McCarty, J. H.
Right arrow Articles by Hynes, R. O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McCarty, J. H.
Right arrow Articles by Hynes, R. O.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Research article

Selective ablation of {alpha}v integrins in the central nervous system leads to cerebral hemorrhage, seizures, axonal degeneration and premature death


Joseph H. McCarty, Adam Lacy-Hulbert, Alain Charest, Roderick T. Bronson, Denise Crowley, David Housman, John Savill, Jürgen Roes, and Richard O. Hynes*
* Author for correspondence (e-mail: rohynes{at}mit.edu)

Mouse embryos genetically null for all {alpha}v integrins develop intracerebral hemorrhage owing to defective interactions between blood vessels and brain parenchymal cells. Here, we have used conditional knockout technology to address whether the cerebral hemorrhage is due to primary defects in vascular or neural cell types. We show that ablating {alpha}v expression in the vascular endothelium has no detectable effect on cerebral blood vessel development, whereas deletion of {alpha}v expression in central nervous system glial cells leads to embryonic and neonatal cerebral hemorrhage. Conditional deletion of {alpha}v integrin in both central nervous system glia and neurons also leads to cerebral hemorrhage, but additionally to severe neurological defects. Approximately 30% of these mutants develop seizures and die by 4 weeks of age. The remaining mutants survive for several months, but develop axonal deterioration in the spinal cord and cerebellum, leading to ataxia and loss of hindlimb coordination. Collectively, these data provide evidence that {alpha}v integrins on embryonic central nervous system neural cells, particularly glia, are necessary for proper cerebral blood vessel development, and also reveal a novel function for {alpha}v integrins expressed on axons in the postnatal central nervous system.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 Am. J. Pathol.Home page
S. L. Nishimura
Integrin-Mediated Transforming Growth Factor-{beta} Activation, a Potential Therapeutic Target in Fibrogenic Disorders
Am. J. Pathol., October 1, 2009; 175(4): 1362 - 1370.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
A. K. Mobley, J. H. Tchaicha, J. Shin, M. G. Hossain, and J. H. McCarty
{beta}8 integrin regulates neurogenesis and neurovascular homeostasis in the adult brain
J. Cell Sci., June 1, 2009; 122(11): 1842 - 1851.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. Stanco, C. Szekeres, N. Patel, S. Rao, K. Campbell, J. A. Kreidberg, F. Polleux, and E. S. Anton
Netrin-1-{alpha}3{beta}1 integrin interactions regulate the migration of interneurons through the cortical marginal zone
PNAS, May 5, 2009; 106(18): 7595 - 7600.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
P. Aluwihare, Z. Mu, Z. Zhao, D. Yu, P. H. Weinreb, G. S. Horan, S. M. Violette, and J. S. Munger
Mice that lack activity of {alpha}v{beta}6- and {alpha}v{beta}8-integrins reproduce the abnormalities of Tgfb1- and Tgfb3-null mice
J. Cell Sci., January 15, 2009; 122(2): 227 - 232.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J. H. McCarty
{alpha}v Integrins Lead the Way for Colorectal Metastases
Clin. Cancer Res., October 15, 2008; 14(20): 6351 - 6353.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
R. Silva, G. D'Amico, K. M. Hodivala-Dilke, and L. E. Reynolds
Integrins: The Keys to Unlocking Angiogenesis
Arterioscler Thromb Vasc Biol, October 1, 2008; 28(10): 1703 - 1713.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
J. H. McCarty, M. Barry, D. Crowley, R. T. Bronson, A. Lacy-Hulbert, and R. O. Hynes
Genetic Ablation of {alpha}v Integrins in Epithelial Cells of the Eyelid Skin and Conjunctiva Leads to Squamous Cell Carcinoma
Am. J. Pathol., June 1, 2008; 172(6): 1740 - 1747.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
R. Belvindrah, D. Graus-Porta, S. Goebbels, K.-A. Nave, and U. Muller
1 Integrins in Radial Glia But Not in Migrating Neurons Are Essential for the Formation of Cell Layers in the Cerebral Cortex
J. Neurosci., December 12, 2007; 27(50): 13854 - 13865.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
A. Kostic, J. Sap, and M. P. Sheetz
RPTP{alpha} is required for rigidity-dependent inhibition of extension and differentiation of hippocampal neurons
J. Cell Sci., November 1, 2007; 120(21): 3895 - 3904.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. Lacy-Hulbert, A. M. Smith, H. Tissire, M. Barry, D. Crowley, R. T. Bronson, J. T. Roes, J. S. Savill, and R. O. Hynes
Ulcerative colitis and autoimmunity induced by loss of myeloid {alpha}v integrins
PNAS, October 2, 2007; 104(40): 15823 - 15828.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. Liu, S. D. Fraser, P. W. Faloon, E. L. Rollins, J. Vom Berg, O. Starovic-Subota, A. L. Laliberte, J.-N. Chen, F. C. Serluca, and S. J. Childs
A betaPix Pak2a signaling pathway regulates cerebral vascular stability in zebrafish
PNAS, August 28, 2007; 104(35): 13990 - 13995.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
K. R. Wagner
Modeling Intracerebal Hemorrhage: Glutamate, Nuclear Factor-{kappa}B Signaling and Cytokines
Stroke, February 1, 2007; 38(2): 753 - 758.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
S. Maubant, D. Saint-Dizier, M. Boutillon, F. Perron-Sierra, P. J. Casara, J. A. Hickman, G. C. Tucker, and E. Van Obberghen-Schilling
Blockade of {alpha}vbeta3 and {alpha}vbeta5 integrins by RGD mimetics induces anoikis and not integrin-mediated death in human endothelial cells
Blood, November 1, 2006; 108(9): 3035 - 3044.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
G. J. del Zoppo and R. Milner
Integrin-Matrix Interactions in the Cerebral Microvasculature
Arterioscler Thromb Vasc Biol, September 1, 2006; 26(9): 1966 - 1975.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
N. Haubst, E. Georges-Labouesse, A. De Arcangelis, U. Mayer, and M. Gotz
Basement membrane attachment is dispensable for radial glial cell fate and for proliferation, but affects positioning of neuronal subtypes
Development, August 15, 2006; 133(16): 3245 - 3254.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
J. Araya, S. Cambier, A. Morris, W. Finkbeiner, and S. L. Nishimura
Integrin-Mediated Transforming Growth Factor-{beta} Activation Regulates Homeostasis of the Pulmonary Epithelial-Mesenchymal Trophic Unit
Am. J. Pathol., August 1, 2006; 169(2): 405 - 415.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Lakhe-Reddy, S. Khan, M. Konieczkowski, G. Jarad, K. L. Wu, L. F. Reichardt, Y. Takai, L. A. Bruggeman, B. Wang, J. R. Sedor, et al.
beta8 Integrin Binds Rho GDP Dissociation Inhibitor-1 and Activates Rac1 to Inhibit Mesangial Cell Myofibroblast Differentiation
J. Biol. Chem., July 14, 2006; 281(28): 19688 - 19699.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Maglott, P. Bartik, S. Cosgun, P. Klotz, P. Ronde, G. Fuhrmann, K. Takeda, S. Martin, and M. Dontenwill
The Small {alpha}5{beta}1 Integrin Antagonist, SJ749, Reduces Proliferation and Clonogenicity of Human Astrocytoma Cells.
Cancer Res., June 15, 2006; 66(12): 6002 - 6007.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
A. Seker, K. L. Pricola, B. Guclu, A. K. Ozturk, A. Louvi, and M. Gunel
CCM2 Expression Parallels That of CCM1
Stroke, February 1, 2006; 37(2): 518 - 523.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
J. M. Proctor, K. Zang, D. Wang, R. Wang, and L. F. Reichardt
Vascular Development of the Brain Requires {beta}8 Integrin Expression in the Neuroepithelium
J. Neurosci., October 26, 2005; 25(43): 9940 - 9948.
[Abstract] [Full Text] [PDF]

Home page
 Cereb CortexHome page
R. S. Schmid, R. Jo, S. Shelton, J. A. Kreidberg, and E. S. Anton
Reelin, Integrin and Dab1 Interactions during Embryonic Cerebral Cortical Development
Cereb Cortex, October 1, 2005; 15(10): 1632 - 1636.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. H. McCarty, A. A. Cook, and R. O. Hynes
An interaction between {alpha}v{beta}8 integrin and Band 4.1B via a highly conserved region of the Band 4.1 C-terminal domain
PNAS, September 20, 2005; 102(38): 13479 - 13483.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
S. Cambier, S. Gline, D. Mu, R. Collins, J. Araya, G. Dolganov, S. Einheber, N. Boudreau, and S. L. Nishimura
Integrin {alpha}v{beta}8-Mediated Activation of Transforming Growth Factor-{beta} by Perivascular Astrocytes: An Angiogenic Control Switch
Am. J. Pathol., June 1, 2005; 166(6): 1883 - 1894.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2004