scholarly journals Evaluating the Role of Wnt Signal Transduction in Promoting the Development of the Heart

2007 ◽  
Vol 7 ◽  
pp. 161-176 ◽  
Author(s):  
Leonard M. Eisenberg ◽  
Carol A. Eisenberg
Keyword(s):  
Signal Transduction ◽  
Planar Cell Polarity ◽  
Cardiac Development ◽  
Experimental Studies ◽  
Stem Cell Differentiation ◽  
Wnt Proteins ◽  
And Function ◽  
Canonical Wnt ◽  
Wnt Signal

Wnts are a family of secreted signaling proteins that are encoded by 19 distinct genes in the vertebrate genome. These molecules initiate several signal transduction pathways: the canonical Wnt, Wnt/Ca2+, and Wnt/planar cell polarity pathways. Wnt proteins have major impact on embryonic development, tumor progression, and stem cell differentiation. Wnt signal transduction also influences the formation of the heart, yet many issues concerning the involvement of Wnt regulation in initiating cardiac development remain unresolved. In this review, we will examine the published record to discern (a) what has been shown by experimental studies on the participation of Wnt signaling in cardiogenesis, and (b) what are the important questions that need to be addressed to understand the importance and function of Wnt signal transduction in facilitating the development of the heart.

scholarly journals Centromere Protein B Null Mice are Mitotically and Meiotically Normal but Have Lower Body and Testis Weights

1998 ◽  
Vol 141 (2) ◽  
pp. 309-319 ◽  
Author(s):  
Damien F. Hudson ◽  
Kerry J. Fowler ◽  
Elizabeth Earle ◽  
Richard Saffery ◽  
Paul Kalitsis ◽  
...  
Keyword(s):  
Cell Cycle Progression ◽  
Mammalian Species ◽  
Experimental Studies ◽  
Conflicting Evidence ◽  
Body Weights ◽  
Reduced Rate ◽  
And Function ◽  
Centromere Assembly ◽  
Mitosis And Meiosis

CENP-B is a constitutive centromere DNA-binding protein that is conserved in a number of mammalian species and in yeast. Despite this conservation, earlier cytological and indirect experimental studies have provided conflicting evidence concerning the role of this protein in mitosis. The requirement of this protein in meiosis has also not previously been described. To resolve these uncertainties, we used targeted disruption of the Cenpb gene in mouse to study the functional significance of this protein in mitosis and meiosis. Male and female Cenpb null mice have normal body weights at birth and at weaning, but these subsequently lag behind those of the heterozygous and wild-type animals. The weight and sperm content of the testes of Cenpb null mice are also significantly decreased. Otherwise, the animals appear developmentally and reproductively normal. Cytogenetic fluorescence-activated cell sorting and histological analyses of somatic and germline tissues revealed no abnormality. These results indicate that Cenpb is not essential for mitosis or meiosis, although the observed weight reduction raises the possibility that Cenpb deficiency may subtly affect some aspects of centromere assembly and function, and result in reduced rate of cell cycle progression, efficiency of microtubule capture, and/or chromosome movement. A model for a functional redundancy of this protein is presented.

scholarly journals Extracellular Vesicles and Thrombosis: Update on the Clinical and Experimental Evidence

2021 ◽  
Vol 22 (17) ◽  
pp. 9317
Author(s):  
Konstantinos Zifkos ◽  
Christophe Dubois ◽  
Katrin Schäfer
Keyword(s):  
Experimental Evidence ◽  
Extracellular Vesicles ◽  
Thrombus Formation ◽  
Experimental Studies ◽  
Cell Types ◽  
Heterogenous Group ◽  
Clearance Mechanism ◽  
And Function ◽  
Role And Function

Extracellular vesicles (EVs) compose a heterogenous group of membrane-derived particles, including exosomes, microvesicles and apoptotic bodies, which are released into the extracellular environment in response to proinflammatory or proapoptotic stimuli. From earlier studies suggesting that EV shedding constitutes a cellular clearance mechanism, it has become evident that EV formation, secretion and uptake represent important mechanisms of intercellular communication and exchange of a wide variety of molecules, with relevance in both physiological and pathological situations. The putative role of EVs in hemostasis and thrombosis is supported by clinical and experimental studies unraveling how these cell-derived structures affect clot formation (and resolution). From those studies, it has become clear that the prothrombotic effects of EVs are not restricted to the exposure of tissue factor (TF) and phosphatidylserines (PS), but also involve multiplication of procoagulant surfaces, cross-linking of different cellular players at the site of injury and transfer of activation signals to other cell types. Here, we summarize the existing and novel clinical and experimental evidence on the role and function of EVs during arterial and venous thrombus formation and how they may be used as biomarkers as well as therapeutic vectors.

New Insights about Regulatory T Cells Distribution and Function with Exercise: The Role of Immunometabolism

2020 ◽  
Vol 26 (9) ◽  
pp. 979-990 ◽  
Author(s):  
Gilson P. Dorneles ◽  
Aline A.Z. dos Passos ◽  
Pedro R.T. Romão ◽  
Alessandra Peres
Keyword(s):  
T Cells ◽  
Chronic Diseases ◽  
Experimental Studies ◽  
Treg Cells ◽  
Metabolic Phenotype ◽  
Acid Oxidation ◽  
Low Grade ◽  
And Function ◽  
Low Grade Inflammation

A lack of physical activity is linked to the development of many chronic diseases through a chronic low-grade inflammation state. It is now well accepted that the immune system plays a central role in the development of several chronic diseases, including insulin resistance, type 2 diabetes, atherosclerosis, heart failure and certain types of cancer. Exercise elicits a strong anti-inflammatory response independently of weight loss and can be a useful non-pharmacologic strategy to counteract the low-grade inflammation. The CD4+CD25+CD127- FoxP3+ Regulatory T (Treg) cells are a unique subset of helper T-cells, which regulate immune response and establish self-tolerance through the secretion of immunoregulatory cytokines, such as IL-10 and TGF-β, and the suppression of the function and activity of many immune effector cells (including monocytes/macrophages, dendritic cells, CD4+ and CD8+ T cells, and Natural Killers). The metabolic phenotype of Tregs are regulated by the transcription factor Foxp3, providing flexibility in fuel choice, but a preference for higher fatty acid oxidation. In this review, we focus on the mechanisms by which exercise - both acute and chronic - exerts its antiinflammatory effects through Treg cells mobilization. Furthermore, we discuss the implications of immunometabolic changes during exercise for the modulation of Treg phenotype and its immunosuppressive function. This narrative review focuses on the current knowledge regarding the role of Treg cells in the context of acute and chronic exercise using data from observational and experimental studies. Emerging evidence suggests that the immunomodulatory effects of exercise are mediated by the ability of exercise to adjust and improve Tregs number and function.

scholarly journals Bearing My Heart: The Role of Extracellular Matrix on Cardiac Development, Homeostasis, and Injury Response

2021 ◽  
Vol 8 ◽  
Author(s):  
Ana Catarina Silva ◽  
Cassilda Pereira ◽  
Ana Catarina R. G. Fonseca ◽  
Perpétua Pinto-do-Ó ◽  
Diana S. Nascimento
Keyword(s):  
Extracellular Matrix ◽  
Cardiac Development ◽  
Cardiac Cells ◽  
Cellular Processes ◽  
Fibrotic Tissue ◽  
Short Period ◽  
And Function ◽  
Regenerative Therapies ◽  
The Impact

The extracellular matrix (ECM) is an essential component of the heart that imparts fundamental cellular processes during organ development and homeostasis. Most cardiovascular diseases involve severe remodeling of the ECM, culminating in the formation of fibrotic tissue that is deleterious to organ function. Treatment schemes effective at managing fibrosis and promoting physiological ECM repair are not yet in reach. Of note, the composition of the cardiac ECM changes significantly in a short period after birth, concurrent with the loss of the regenerative capacity of the heart. This highlights the importance of understanding ECM composition and function headed for the development of more efficient therapies. In this review, we explore the impact of ECM alterations, throughout heart ontogeny and disease, on cardiac cells and debate available approaches to deeper insights on cell–ECM interactions, toward the design of new regenerative therapies.

scholarly journals Re-Evaluating the Role of Frat in Wnt-Signal Transduction

Cell Cycle ◽  
2005 ◽  
Vol 4 (8) ◽  
pp. 4065-4072 ◽  
Author(s):  
Renée van Amerongen ◽  
Anton Berns
Keyword(s):  
Signal Transduction ◽  
Wnt Signal

scholarly journals β-catenin is a central mediator of pro-fibrotic Wnt signaling in systemic sclerosis

2012 ◽  
Vol 71 (5) ◽  
pp. 761-767 ◽  
Author(s):  
Christian Beyer ◽  
Amelie Schramm ◽  
Alfiya Akhmetshina ◽  
Clara Dees ◽  
Trayana Kireva ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Wnt Signaling ◽  
Nuclear Accumulation ◽  
Central Component ◽  
Fibroblast Activation ◽  
Dermal Fibrosis ◽  
Wnt Proteins ◽  
Nuclear Levels ◽  
Canonical Wnt

ObjectivesPathologic fibroblast activation drives fibrosis of the skin and internal organs in patients with systemic sclerosis (SSc). β-catenin is an integral part of adherens junctions and a central component of canonical Wnt signaling. Here, the authors addressed the role of β-catenin in fibroblasts for the development of SSc dermal fibrosis.MethodsNuclear accumulation of β-catenin in fibroblasts was assessed by triple staining for β-catenin, prolyl-4-hydroxylase-β and 4′,6-diamidino-2-phenylindole (DAPI). The expression of Wnt proteins in the skin was analysed by real-time PCR and immunohistochemistry. Mice with fibroblast-specific stabilisation or fibroblast-specific depletion were used to evaluate the role of β-catenin in fibrosis.ResultsThe auhors found significantly increased nuclear levels of β-catenin in fibroblasts in SSc skin compared to fibroblasts in the skin of healthy individuals. The accumulation of β-catenin resulted from increased expression of Wnt-1 and Wnt-10b in SSc. The authors further showed that the nuclear accumulation of β-catenin has direct implications for the development of fibrosis: Mice with fibroblast-specific stabilisation of β-catenin rapidly developed fibrosis within 2 weeks with dermal thickening, accumulation of collagen and differentiation of resting fibroblasts into myofibroblasts. By contrast, fibroblast-specific deletion of β-catenin significantly reduced bleomycin-induced dermal fibrosis.ConclusionsThe present study findings identify β-catenin as a key player of fibroblast activation and tissue fibrosis in SSc. Although further translational studies are necessary to test the efficacy and tolerability of β-catenin/Wnt inhibition in SSc, the present findings may have clinical implications, because selective inhibitors of β-catenin/Wnt signaling have recently entered clinical trials.

scholarly journals The Wnt/Planar Cell Polarity Signaling Pathway Contributes to the Integrity of Tight Junctions in Brain Endothelial Cells

2013 ◽  
Vol 34 (3) ◽  
pp. 433-440 ◽  
Author(s):  
Cédric Artus ◽  
Fabienne Glacial ◽  
Kayathiri Ganeshamoorthy ◽  
Nicole Ziegler ◽  
Maeva Godet ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Signaling Pathway ◽  
Tight Junctions ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Osmotic Shock ◽  
Brain Endothelial Cells ◽  
Wnt Proteins ◽  
Mouse Brain Endothelial Cells ◽  
Canonical Wnt

Wnt morphogens released by neural precursor cells were recently reported to control blood–brain barrier (BBB) formation during development. Indeed, in mouse brain endothelial cells, activation of the Wnt/ β-catenin signaling pathway, also known as the canonical Wnt pathway, was shown to stabilize endothelial tight junctions (TJs) through transcriptional regulation of the expression of TJ proteins. Because Wnt proteins activate several distinct β-catenin-dependent and independent signaling pathways, this study was designed to assess whether the noncanonical Wnt/Par/aPKC planar cell polarity (PCP) pathway might also control TJ integrity in brain endothelial cells. First we established, in the hCMEC/D3 human brain endothelial cell line, that the Par/aPKC PCP complex colocalizes with TJs and controls apicobasal polarization. Second, using an siRNA approach, we showed that the Par/aPKC PCP complex regulates TJ stability and reassembling after osmotic shock. Finally, we provided evidence that Wnt5a signals in hCMEC/D3 cells through activation of the Par/aPKC PCP complex, independently of the Wnt canonical β-catenin-dependent pathway and significantly contributes to TJ integrity and endothelial apicobasal polarity. In conclusion, this study suggests that the Wnt/Par/aPKC PCP pathway, in addition to the Wnt/ β-catenin canonical pathway, is a key regulator of the BBB.

The role of the non-canonical Wnt–planar cell polarity pathway in neural crest migration

2013 ◽  
Vol 457 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Roberto Mayor ◽  
Eric Theveneau
Keyword(s):  
Neural Crest ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Neural Crest Cells ◽  
Contact Inhibition ◽  
Stem Cell Population ◽  
Planar Cell Polarity Pathway ◽  
Canonical Wnt ◽  
Neural Crest Migration

The neural crest is an embryonic stem cell population whose migratory behaviour has been likened to malignant invasion. The neural crest, as does cancer, undergoes an epithelial-to-mesenchymal transition and migrates to colonize almost all the tissues of the embryo. Neural crest cells exhibit collective cell migration, moving in streams of high directionality. The migratory neural crest streams are kept in shape by the presence of negative signals in their vicinity. The directionality of the migrating neural crest is achieved by contact-dependent cell polarization, in a phenomenon called contact inhibition of locomotion. Two cells experiencing contact inhibition of locomotion move away from each other after collision. However, if the cell density is high only cells exposed to a free edge can migrate away from the cluster leading to the directional migration of the whole group. Recent work performed in chicks, zebrafish and frogs has shown that the non-canonical Wnt–PCP (planar cell polarity) pathway plays a major role in neural crest migration. PCP signalling controls contact inhibition of locomotion between neural crest cells by localizing different PCP proteins at the site of cell contact during collision and locally regulating the activity of Rho GTPases. Upon collision RhoA (ras homologue family member A) is activated, whereas Rac1 is inhibited at the contact between two migrating neural crest cells, leading to the collapse of protrusions and the migration of cells away from one another. The present review summarizes the mechanisms that control neural crest migration and focuses on the role of non-canonical Wnt or PCP signalling in this process.

scholarly journals Mouse Axin and Axin2/Conductin Proteins Are Functionally Equivalent In Vivo

2005 ◽  
Vol 25 (11) ◽  
pp. 4371-4376 ◽  
Author(s):  
Ian V. Chia ◽  
Frank Costantini
Keyword(s):  
Signal Transduction ◽  
Wnt Signaling ◽  
Functional Equivalence ◽  
Central Component ◽  
Related Protein ◽  
Early Embryonic Lethality ◽  
Craniofacial Defects ◽  
Canonical Wnt ◽  
Wnt Signal

ABSTRACT Axin is a central component of the canonical Wnt signal transduction machinery, serving as a scaffold for the β-catenin destruction complex. The related protein Axin2/Conductin, although less extensively studied, is thought to perform similar functions. Loss of Axin causes early embryonic lethality, while Axin2-null mice are viable but have craniofacial defects. Mutations in either gene contribute to cancer in humans. The lack of redundancy between Axin and Axin2 could be due to their different modes of expression: while Axin is expressed ubiquitously, Axin2 is expressed in tissue- and developmental-stage-specific patterns, and its transcription is induced by canonical Wnt signaling. Alternatively, the two proteins might have partially different functions, a hypothesis supported by the observation that they differ in their subcellular localizations in colon epithelial cells. To test the functional equivalence of Axin and Axin2 in vivo, we generated knockin mice in which the Axin gene was replaced with Myc-tagged Axin or Axin2 cDNA. Mice homozygous for the resulting alleles, Axin Ax or Axin Ax2 , express no endogenous Axin but express either Myc-Axin or Myc-Axin2 under the control of the Axin locus. Both Axin Ax/Ax and Axin Ax2/Ax2 homozygotes are apparently normal and fertile, demonstrating that the Axin and Axin2 proteins are functionally equivalent.

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