The conditional inactivation of the β-catenin gene in endothelial cells causes a defective vascular pattern and increased vascular fragility

Cattelino, Anna; Liebner, Stefan; Gallini, R; Zanetti, Adriana; Balconi, Giovanna; Corsi, Alessandro; Bianco, Patrizia Del; Wolburg, Hartwig; Moore, Robert H.; Boussadia, Oréda; Kemler, Rolf; Dejana, Elisabetta

doi:10.1083/jcb.200212157

Cited by 301 publications

(266 citation statements)

References 55 publications

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“…We did not observe changes in ␤-catenin subcellular localization during differentiation of C2 cells (data not shown). Moreover, the ␤-catenin knockdown was compensated by an augmentation in ␥-catenin/plakoglobin, substituting for ␤-catenin at the membrane (56,57). These observations suggest that cytosolic ␤-catenin might act negatively on myogenic differentiation through a mechanism independent of N-cadherin adhesion as previously suggested for ␤-catenin function during tumor cell proliferation (45,46).…”

Section: Discussionsupporting

confidence: 68%

N-cadherin Activation Substitutes for the Cell Contact Control in Cell Cycle Arrest and Myogenic Differentiation

Gavard

Marthiens

Monnet

et al. 2004

Journal of Biological Chemistry

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N-cadherin is expressed throughout skeletal myogenesis and has been proposed to be involved in the differentiation program of myogenic precursors. Here, we further characterize the N-cadherin involvement and its mechanism of action at the onset of differentiation, through controlled N-cadherin activation by plating isolated C2 myoblasts on surfaces coated with a chimeric Ncad-Fc homophilic ligand (N-cadherin ectodomain fused to the immunoglobulin G Fc fragment). We show that N-cadherin activation substitutes for the cell density in myogenic differentiation by promoting myogenin and troponin T expression. In addition, N-cadherin adhesion participates to the associated cell cycle arrest through the nuclear accumulation of cyclin-dependent kinase inhibitors p21 and p27. Mouse primary myoblast cultures exhibited similar responses to N-cadherin as C2 cells. RNA interference knockdowns of the N-cadherinassociated cytoplasmic proteins p120 and ␤-catenin produced opposite effects on the differentiation pathway. p120 silencing resulted in a decreased myogenic differentiation, associated with a reduction in cadherin-catenin content, which may explain its action on myogenic differentiation. ␤-Catenin silencing led to a stimulatory effect on myogenin expression, without any effect on cell cycle. Our results demonstrate that N-cadherin adhesion may account for cell-cell contact-dependent cell cycle arrest and differentiation of myogenic cells, involving regulation through p120 and ␤-catenins.

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Section: Discussionsupporting

confidence: 68%

N-cadherin Activation Substitutes for the Cell Contact Control in Cell Cycle Arrest and Myogenic Differentiation

Gavard

Marthiens

Monnet

et al. 2004

Journal of Biological Chemistry

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“…Reduced migration, inability to undergo capillary morphogenesis in matrigel (Kondo et al, 2007) Total Mice viable, defects in retinal vasculature (Dimaio et al, 2008) β-catenin Cell-cell adhesion Conditional EC-specific knockout Death between E11.5 and E13.5; impaired vascular patterning in the head, vitelline and umbilical vessels, and placenta (Cattelino et al, 2003) N-cadherin Cell-cell adhesion Conditional NC specific Defects in remodeling of cardiac outflow tract (Luo et al, 2006) Total Death by E10 (Radice et al, 1997) Conditional EC specific Death at midgestation, severe vascular defects, decrease of VE-cadherin (Luo and Radice, 2005) E-cadherin Cell-cell adhesion Total Early lethality, fail to form trophectoderm. (Larue et al, 1994) VE-cadherin Cell-cell adhesion Total Death at E9.5, endothelial cells are assembled in vascular plexi, but their subsequent remodeling and maturation are impaired.…”

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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“…Because it is difficult to study postnatal endochondral ossification using canonical Wnt pathway knockout approaches because of lethality, (11,(13)(14)(15) we used a Dkk1 and Dkk2 misexpression strategy, generating cell-specific (chondrocyte, hypertrophic chondrocyte, endothelial cell) transgenic (TG) mice to elucidate the mechanisms that couple cartilage development and angiogenesis. We report here that only endothelial cell-specific Dkk1 TG mice showed defects in endochondral ossification.…”

Section: Introductionmentioning

confidence: 99%

Misexpression of Dickkopf-1 in endothelial cells, but not in chondrocytes or hypertrophic chondrocytes, causes defects in endochondral ossification

Oh¹,

Ryu²,

Jeon³

et al. 2012

Journal of Bone and Mineral Research

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Developing cartilage serves as a template for long-bone development during endochondral ossification. Although the coupling of cartilage and bone development with angiogenesis is an important regulatory step for endochondral ossification, the molecular mechanisms are poorly understood. One possible mechanism involves the action of Dickkopf (DKK), which is a family of soluble canonical Wnt antagonists with four members (DKK1-4). We initially observed opposite expression patterns of Dkk1 and Dkk2 during angiogenesis and chondrocyte differentiation: downregulation of Dkk1 and upregulation of Dkk2. We examined the in vivo role of Dkk1 and Dkk2 in linking cartilage/bone development and angiogenesis by generating transgenic (TG) mice that specifically express Dkk1 or Dkk2 in chondrocytes, hypertrophic chondrocytes, or endothelial cells. Despite specific expression pattern during cartilage development, chondrocyte-and hypertrophic chondrocyte-specific Dkk1 and Dkk2 TG mice showed normal developmental phenotypes. However, Dkk1 misexpression in endothelial cells resulted in defects of endochondral ossification and reduced skeletal size. The defects are caused by the inhibition of angiogenesis in developing bone and subsequent inhibition of apoptosis of hypertrophic chondrocytes and cartilage resorption. ß

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The conditional inactivation of the β-catenin gene in endothelial cells causes a defective vascular pattern and increased vascular fragility

Cited by 301 publications

References 55 publications

N-cadherin Activation Substitutes for the Cell Contact Control in Cell Cycle Arrest and Myogenic Differentiation

N-cadherin Activation Substitutes for the Cell Contact Control in Cell Cycle Arrest and Myogenic Differentiation

Cell biology of embryonic migration

Misexpression of Dickkopf-1 in endothelial cells, but not in chondrocytes or hypertrophic chondrocytes, causes defects in endochondral ossification

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