β3-integrin–deficient mice are a model for Glanzmann thrombasthenia showing placental defects and reduced survival

Hodivala‐Dilke, Kairbaan; McHugh, Kevin P.; Tsakiris, Dimitrios Α.; Rayburn, Helen; Crowley, Denise; Ullman-Culleré, Mollie; Ross, F. Patrick; Coller, Barry S.; Teitelbaum, Steven L.; Hynes, Richard O.

doi:10.1172/jci5487

Cited by 693 publications

(623 citation statements)

References 50 publications

(33 reference statements)

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“…Reduced neural crest cell motility (Breau et al, 2006) β3 integrin Integrins Total Defects in platelet aggregation and clot retraction, hemmorhages, postnatal anemia, and reduced survival (Hodivala-Dilke, 1999) β8 integrin Integrins Total Embryonic or perinatal lethality with profound defects in vascular development, insufficient vascularization of the placenta and yolk sac (Zhu et al, 2002) VCAM-1 Integrins Total Embrynic lethality at E10-12, abnormal placental development (Gurtner et al, 1995) Syndecan-4 Extracellular matrix Total Blood vessel defects in the placenta; defects in angiogenesis and wound repair (Echtermeyer, 2001;Ishiguro, 2000;Kojima, 2002) N-syndecan Extracellular matrix Total Impaired neural migration in the developing brain (Hienola et al, 2006) Perlecan Extracellular matrix Total Defects in heart integrity, invasion of brain tissue into the overlaying ectoderm, severe defect in cartilage, cleft palates and death shortly after birth from respiratory failure. (Costell et al, 1999) Tenascin C Extracellular matrix Total NC cells fail to disperse laterally (Tucker, 2001) Laminin γ1 Extracellular matrix Total Death at E5.5, lack of basement membranes (Smyth et al, 1999) Laminin β2 Extracellular matrix Total Postnatal death between P15-30, neuromuscular junctions and glomerular defects (Noakes et al, 1995a;Noakes et al, 1995b;Patton et al, 1997) Laminin α2 Extracellular matrix Total Death by 5 weeks postnatal, severe muscular dystrophy and peripheral neurophathy (Miyagoe et al, 1997) Laminin α2 (dy/dy) Extracellular matrix Spontaneous Adult lethality, severe muscular dystrophy and peripheral nerve dysmyelination (Patton et al, 1999;Patton et al, 1997) Laminin α3 Extracellular matrix Total Death at P2-3, epithelial adhesion defect (Ryan et al, 1999) Laminin α4 Extracellular matrix Total Transient microvascular defect with hemorrhages and misalignment of neuromuscular junctions (Patton et al, 2001;Thyboll et al, 2002) Laminin α5 Extracellular matrix Total Death at E14-E17, with placental vessel, neural (Miner et al, 1998;Miner and Li, 2000) Protein Function Type Phenotype Reference tube, limb, and kidney defects Fibronectin Extracellular matrix Total Death before E14.5, shortened anterior-posterior axes, deformed neural tubes, and defects in mesodermally derived tissues.…”

Section: Note On Nomenclaturementioning

confidence: 99%

Cell biology of embryonic migration

Kurosaka¹,

Kashina²

2008

Birth Defects Research Pt C

111

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Cell migration is an evolutionarily conserved mechanism that underlies the development and functioning of uni-and multicellular organisms and takes place in normal and pathogenic processes, including various events of embryogenesis, wound healing, immune response, cancer metastases, and angiogenesis. Despite the differences in the cell types that take part in different migratory events, it is believed that all of these migrations occur by similar molecular mechanisms, whose major components have been functionally conserved in evolution and whose perturbation leads to severe developmental defects. These mechanisms involve intricate cytoskeleton-based molecular machines that can sense the environment, respond to signals, and modulate the entire cell behavior. A big question that has concerned the researchers for decades relates to the coordination of cell migration in situ and its relation to the intracellular aspects of the cell migratory mechanisms. Traditionally, this question has been addressed by researchers that considered the intra-and extracellular mechanisms driving migration in separate sets of studies. As more data accumulate researchers are now able to integrate all of the available information and consider the intracellular mechanisms of cell migration in the context of the developing organisms that contain additional levels of complexity provided by extracellular regulation. This review provides a broad summary of the existing and emerging data in the cell and developmental biology fields regarding cell migration during development.

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Section: Note On Nomenclaturementioning

confidence: 99%

Cell biology of embryonic migration

Kurosaka¹,

Kashina²

2008

Birth Defects Research Pt C

111

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“…When this integrin is activated, it binds fibrinogen and thereby promotes the formation of platelet aggregates that close a wound. In line with such an important function, null mutations in the genes encoding αIIb or β3 cause a bleeding disorder termed Glanzmann thrombasthenia in mice as well as in human patients [112,113]. The fact that platelet numbers are not affected in the β3 null mice shows that β3 integrins are not critically involved in the development of the megakaryocytic lineage.…”

Section: Haematopoietic Cellsmentioning

confidence: 99%

Integrins in regulation of tissue development and function

Danen¹,

Sonnenberg²

2003

The Journal of Pathology

228

171

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Cell adhesion is indispensable for embryonic development and for proper tissue function. In metazoans, integrins are the major adhesion receptors that connect cells to components of the extracellular matrix. Integrins are implicated in assembly of extracellular matrices, cell adhesion and migration on extracellular matrices, and in vertebrates (in which the integrin family has expanded) they can also mediate cell-cell adhesion. Furthermore, integrinmediated adhesion can modulate many different signal transduction cascades and support cell survival, proliferation, and influence the expression of differentiation-related genes. In this review we briefly explain how integrins can affect so many different aspects of cell behavior and discuss evidence for roles of integrins in tissue development, function, and disease.

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“…This finding was supported by mice lacking a functional 3 subunit, which did not show evidence for perturbation of vasculogenesis and angiogenesis. 38 The development of blood vessels seemed to be normal in those mice, suggesting that reduced v 3 levels could be compensated by other v integrins as, e.g., the related v 5. In contrast, v-deficient mice embryos had a lethal phenotype due to a perturbation of the blood vessel development in the brain.…”

Section: Cancer Gene Therapymentioning

confidence: 95%

Inhibition of angiogenesis in vitro by αv integrin–directed antisense oligonucleotides

Kronenwett

Graf

Nedbal³

et al. 2002

Cancer Gene Ther

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The integrin v 3 plays a central role in angiogenesis. In this study, we used antisense oligodeoxyribonucleotides ( ONs ) directed against the v subunit of v 3 to inhibit integrin expression. Ten ON sequences, which were selected by systematic alignment of computer -predicted secondary structures of v mRNA, were transfected into human umbilical vein endothelial cells ( HUVECs ). Following stimulation by PMA, five antisense ONs significantly inhibited v mRNA and protein expression in activated HUVEC at a concentration of 0.05 M with complete prevention of PMA -induced v up -regulation by the most potent antisense ON. Inhibition of v expression was associated with significant inhibition of migration of HUVEC by 28% and had no effect on proliferation and apoptosis. Moreover, transfection of antisense ON inhibited the formation of tube -like structures of HUVEC in Matrigel by 44%. In a cell culture model of angiogenesis consisting of a co -culture of endothelial cells with fibroblasts, transfection of antisense ONs resulted in an inhibition of tube formation of 61%. In conclusion, v antisense ONs are potent inhibitors of angiogenesis in vitro. They might, therefore, be a therapeutic alternative to antagonists, which directly bind to v integrins, and might be useful for the treatment of malignant tumors and hematological malignancies.

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β3-integrin–deficient mice are a model for Glanzmann thrombasthenia showing placental defects and reduced survival

Cited by 693 publications

References 50 publications

Cell biology of embryonic migration

Cell biology of embryonic migration

Integrins in regulation of tissue development and function

Inhibition of angiogenesis in vitro by αv integrin–directed antisense oligonucleotides

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