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Investigating The Contribution Of The Notch 1 Signaling Pathway During Vascular Morphogenesis
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Book Synopsis Investigating the Contribution of the Notch 1 Signaling Pathway During Vascular Morphogenesis by : Jackelyn Ann Alva
Download or read book Investigating the Contribution of the Notch 1 Signaling Pathway During Vascular Morphogenesis written by Jackelyn Ann Alva and published by . This book was released on 2006 with total page 328 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Notch Signaling in Vascular Development by : Jennifer Jean Hofmann
Download or read book Notch Signaling in Vascular Development written by Jennifer Jean Hofmann and published by . This book was released on 2009 with total page 390 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis The Role of Notch Signaling in Vascular Development and Homeostasis by :
Download or read book The Role of Notch Signaling in Vascular Development and Homeostasis written by and published by . This book was released on 2007 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The vasculature is essential for the delivery of oxygen and nutrients and the removal of metabolic wastes from tissues of the body. The embryonic vasculature is developed through the processes of vasculogenesis, angiogenesis, and arteriogenesis. Once the vasculature is fully developed and stabilized, the adult vasculature shows very little proliferation or cell death. Nevertheless, the endothelium, which lines the lumen of the blood vessels, is actively involved in the control of vascular tone, permeability, blood flow, coagulation, inflammation and tissue repair. An injury to the endothelium is important for progression of diseases such as atherosclerosis and the sepsis syndrome. The Notch signaling pathway has emerged in the recent decade as an important player in multiple vascular processes and endothelial behaviors. This thesis examines the role of the Notch signaling pathway in embryonic arteriogenesis and endothelial survival signaling. The first part of this thesis investigates the developmental source of vascular smooth muscle cells. This study presents the first in situ observation of an immediate smooth muscle precursor cell present in all embryonic arteries. This Tie1/CD31/VE-cadherin− precursor requires Notch signaling to differentiate into vascular smooth muscle cells and to ensure vascular stability of newly formed arteries. However, Notch activation is not required in the precursor cells to maintain the medial layer of the arteries once the vessel is invested with vascular smooth muscle cells. In the second part of this thesis, the mechanism of Notch-induced endothelial survival signaling is examined. In endothelial cells, Notch signaling activates phosphotidylinositol-3 kinase (PI3K) through up-regulation of a secreted factor. Activity of PI3K is required to offset the parallel apoptotic signaling induced by Notch activation and to maintain endothelial survival through the up-regulation of Slug, a direct Notch target with anti-apoptotic activity. U.
Book Synopsis Examining Post-transcriptional Regulation of the Notch Pathway During Vertebrate Development by : Maurisa Flynn Riley
Download or read book Examining Post-transcriptional Regulation of the Notch Pathway During Vertebrate Development written by Maurisa Flynn Riley and published by . This book was released on 2011 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: The Notch pathway is a highly conserved signaling mechanism used for cell-to-cell communication during development. Errors in this communication system can lead to birth defects and contribute to the development and progression of numerous diseases. The significance of Notch in cardiac development is evident from the identification of human mutations in various Notch pathway members that result in congenital cardiovascular malformations. Despite the importance of Notch signaling in cardiac development, a lack of functional studies examining the molecular mechanisms underlying these Notch implicated malformations represents a significant gap in the field of cardiovascular biology. We identified novel NOTCH1 mutations in patients with cardiac malformations involving the left ventricular outflow tract (LVOT) that reduce ligand-induced signaling through defective intracellular processing of the mutant Notch1 receptor protein. The Notch pathway also functions in a biological clock that is critical for skeletal development during somitogenesis. During somitogenesis, somites bud from the anterior end of the presomitic mesoderm (PSM) to give rise to the axial skeleton, the dermis of the back, and skeletal muscle. This developmental process proves useful for studying the Notch pathway, because in the PSM, Notch oscillations are coordinated, resulting in visible oscillatory expression of genes linked to the clock. Mutations that perturb these oscillations can be easily observed at the level of gene expression, and result in overt skeletal phenotypes that do not affect viability. Proper clock function requires that gene expression of Notch pathway members be tightly controlled during the time period of the clock. One of these oscillatory genes is Lunatic fringe (Lfng), which encodes a glycosyltransferase that modifies the Notch receptor to modulate Notch signaling (Hicks C, 2000). Understanding the mechanisms of Notch regulation in the segmentation clock is an active topic of research with many unanswered questions. We hypothesized that microRNAs (miRNAs), small molecules that regulate gene expression, have a conserved function in the segmentation clock through regulation of oscillatory genes in the Notch pathway. miRNA microarray analysis and RT-PCR identified miRNAs enriched in the mouse PSM. Preventing interactions between one of these miRNAs, miR-125a-5p, and Lfng in vivo leads to abnormal segmentation and perturbs cyclic gene expression in the PSM, indicating that miRNA regulation of Lfng is important for the clock mechanism. This work provides the first evidence supporting a role for miRNAs in the segmentation clock and reveals a novel mechanism of post-transcriptional regulation of oscillatory genes. In addition, since the miRNA microarray revealed a large number of miRNAs either enriched in the PSM or mature somites, future work in the lab will examine the function of these miRNAs in segmentation clock function and somite maturation.
Download or read book Chemokines written by Astrid E. Cardona and published by Humana Press. This book was released on 2013-04-27 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chemokines constitute a large family of structurally similar cytokines that contain a signature of conserved cysteine residues joined by disulfide bridges. Binding of chemokines to specific G protein-coupled receptors followed by downstream signaling defines their biological function. Initially, chemoattraction was the key function linked to chemokines/chemokine receptors; however, in recent years, it has become clear that chemokine ligand-receptor interactions can also modulate cellular activation, survival, and proliferation, among other functions in homeostatic and diseased states. Importantly, major advances in our understanding of chemokine biology have led to chemokine receptors becoming specific therapeutic targets with great potential. In Chemokines: Methods and Protocols, expert researchers provide practical information regarding experimental models and state of the art protocols used to delineate chemokine/chemokine receptor function and their applications in health and disease. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Practical and easy to use, Chemokines: Methods and Protocols aims to reveal key protocols of functional and descriptive chemokine ligand/receptor assays that will be of practical significance to graduate students, post-doctoral fellows, trainees, and researchers in academia and industry.
Book Synopsis Notch Signaling Regulates Myeloid Cell Function and Contribution to Angiogenesis by :
Download or read book Notch Signaling Regulates Myeloid Cell Function and Contribution to Angiogenesis written by and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: We investigated the role of Notch signaling in the vascular microenvironment, with particular attention paid to the vascular consequences of Notch signaling disruption in myeloid cells. We adapted an established in vitro model of angiogenesis to recreate interactions between endothelial sprouts and vascular support cells, including macrophages and vascular pericytes. We found that inflammatory polarization of macrophages increased their ability to foster angiogenesis, and that intact Notch signaling was essential to this phenomenon. We also demonstrated a role for Notch/Jagged1 signaling in the interaction between vascular pericytes and endothelial sprouts, the disruption of which limits the growth and maturation of vessel networks. We have also investigated the role of myeloid Notch signaling in vivo, using a number of developmental and pathological models of angiogenesis. We found that Notch inhibition leads to decreased myeloid cell recruitment to a broad variety of functionally distinct angiogenic sites.
Book Synopsis The Role of Adam10 and Notch1 in the Formation of Organ-specific Vascular Structures by : Krzysztof Glomski
Download or read book The Role of Adam10 and Notch1 in the Formation of Organ-specific Vascular Structures written by Krzysztof Glomski and published by . This book was released on 2012 with total page 356 pages. Available in PDF, EPUB and Kindle. Book excerpt: The primary goal of this thesis was to determine the role of Adam10 in endothelial cells in the context of developmental angiogenesis, pathological neovascularization, and organ-specific vascular morphogenesis, based on literature that demonstrated components of the Notch pathway were important for retinal and embryonic angiogenesis and studies that suggested Adam10 was critical for Notch receptor activation, while little was known about the role of Adam10 in these processes. To accomplish this, conditional knockout mice lacking Adam10 from endothelial cells ( Adam10[delta]EC ) were generated. Adam10[delta]EC mice, unlike previously reported Notch1 endothelial cell knockout mice, survived into adulthood and recapitulated the increased branching and density of retinal vasculature also caused by interfering with Notch signaling. Moreover, A10[delta]EC mice had additional vascular abnormalities, including aberrant subcapsular hepatic veins, enlarged glomeruli, intestinal polyps containing endothelial cell masses, abnormal endochondral ossification, stunted long bone growth, and increased pathological neovascularization following oxygen-induced retinopathy. Interestingly, this phenotype was not exacerbated when Adam17 was inactivated along with Adam10 in endothelial cells, despite reports suggesting that Adam17 might serve a redundant or compensatory role to Adam10 in Notch activation. Lastly, Notch1[delta]EC mice were bred to determine whether abnormalities observed in Adam10[delta]EC were due to the lack of Notch1 receptor activity specifically. Notch1[delta]EC animals displayed several vascular defects that were first observed in Adam10[delta]EC mice, including enlarged veins on the liver and heart, enlarged glomeruli and retardation of long bone growth. However, unlike Adam10[delta]EC mice, Notch1[delta]EC mice had no significant increase in retinal vascular branching or vessel density at postnatal day 5, which was surprising in light of previous reports. The constellation of vascular defects found within Adam10[delta]EC and Notch1[delta]EC mice comprised organ-specific vascular abnormalities never-before described and illustrated that endothelial cell requirements for Notch signaling varies depending on the organ-specific vascular niche in question.
Book Synopsis The Role of Notch Signaling in Vessel Maturation and Stabilization by : Elizabeth Lea Scheppke Smoot
Download or read book The Role of Notch Signaling in Vessel Maturation and Stabilization written by Elizabeth Lea Scheppke Smoot and published by . This book was released on 2011 with total page 105 pages. Available in PDF, EPUB and Kindle. Book excerpt: Vascular development and angiogenesis initially depend on endothelial tip cell invasion, which is followed by a series of maturation steps, including lumen formation and recruitment of perivascular cells. Many studies have shown that Notch signaling is involved throughout embryonic vascular development, including the regulation of tip cell formation, artery/vein patterning, and vascular remodeling. However, the role of Notch signaling in the postnatal vasculature has not been well described. Blocking postnatal Notch results in a highly branched, immature vascular plexus. Vascular plexus maturation is partly regulated by vascular smooth muscle cell (VSMC) coverage, and little is known about the role of Notch in the postnatal perivascular compartment. Therefore, the studies in this dissertation proposed to investigate Notch effectors in VSMCs that modulate vessel maturation during postnatal angiogenesis. To verify that Notch signaling is important for postnatal arterial VSMC coverage and subsequent vessel maturation, the perivascular compartment of pups undergoing retinal angiogenesis was examined following Notch inhibition. This resulted in significantly less arterial VSMC coverage. An angiogenesis-specific microarray panel identified Notch effector genes upregulated in VSMCs in contact with the endothelial Notch ligand Jagged1, which is known to be required for arterial VSMC coverage. One of the upregulated genes was integrin [beta]3, which led to increased surface expression of the integrin heterodimer, [alpha]v[beta]3. Integrin [alpha]v[beta]3 is important for cell adhesion and cell migration. In the vasculature, the only available ligand for [alpha]v[beta]3 is von Willebrand Factor (vWF). Examination of pups undergoing retinal developmental angiogenesis revealed that VSMC coverage co-patterns with accumulation of vWF in the endothelial basement membrane. In a 3-dimensional in vitro tube formation assay, disruption of Notch, [alpha]v[beta]3, or vWF prevented an association between VSMCs and newly formed endothelial tubes. Genetic or pharmacological disruption of Jagged1, [alphav]v[beta]3, or vWF suppressed VSMC coverage of nascent vessels and arterial maturation during vascular development in vivo. Therefore, the findings described in this dissertation define a Notch-mediated interaction between the developing endothelium and VSMCs, leading to adhesion of VSMCs to the endothelial basement membrane and arterial maturation.
Book Synopsis The Role of Notch1 Receptor N-glycosylation in the Transition of Stem Cells to Vascular Smooth Muscle Cells by : Abidemi Olayinka
Download or read book The Role of Notch1 Receptor N-glycosylation in the Transition of Stem Cells to Vascular Smooth Muscle Cells written by Abidemi Olayinka and published by . This book was released on 2018 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cell fate decisions within the vasculature are crucial to the pathogenesis of vascular diseases, including, arteriosclerosis, atherosclerosis and restenosis after angioplasty. Notch signalling is involved in regulating cell fate in vasculature development during embryogenesis resulting in altered cell fate decisions leading to vascular disease. The Notch signalling pathway is highly regulated by a number of mechanisms including glycosylation, a post-translational modification. The main objective of this research work was to define a putative role for N-glycosylation of Notch1 receptor in controlling resident vascular stem cell fate in vitro. Utilising ligand Jagged1 (Jag-1)-induced Notch signalling assay, Quantitative RT-PCR, immunocytochemistry, ectopic expression of Notch1 receptor, siRNA knockdown, pharmacological inhibition and enzyme linked lectin assay (ELLA), alterations in N-glycan decoration of the Notch1 receptor were assessed before the effects on Notch signalling and Notch ligand promotion of myogenic differentiation were evaluated. N-glycosylation of the Notch1 receptor was assessed using ELLA and confirmed the presence of N-glycans on the receptor, an effect that was abrogated following inhibition of glycosyltransferase activity with tunicamycin and Lunatic Fringe (Lfng) knockdown. Jag-1- induced Notch activation increased Notch target gene expression and promoted myogenic differentiation of bone-marrow derived mesenchymal stem cells and resident vascular stem cells. Selective knockdown of the Notch1 receptor in stem cells resulted in a decrease in Jag- 1 stimulated Hey1 Notch1 target gene expression concomitant with a reduction in myogenic differentiation due to decreased smooth muscle differentiation marker expression (Cnn1 protein level and Myh11 mRNA level). Inhibition of N-glycosylation with tunicamycin lead to a down regulation of smooth muscle differentiation marker, Myh11 independent of a reduction in Notch target gene expression. Lfng knockdown lead to a similar significant reduction in Jag-1 induced myogenic differentiation (reduced Myh11 mRNA expression). Collectively, these results suggest that N-glycosylation of Notch1 receptor is involved in Notch signalling leading to altered resident vascular stem cell fate.
Book Synopsis Molecular Mechanism of Congenital Heart Disease and Pulmonary Hypertension by : Toshio Nakanishi
Download or read book Molecular Mechanism of Congenital Heart Disease and Pulmonary Hypertension written by Toshio Nakanishi and published by Springer Nature. This book was released on 2020-02-28 with total page 374 pages. Available in PDF, EPUB and Kindle. Book excerpt: This open access book focuses on the molecular mechanism of congenital heart disease and pulmonary hypertension, offering new insights into the development of pulmonary circulation and the ductus arteriosus. It describes in detail the molecular mechanisms involved in the development and morphogenesis of the heart, lungs and ductus arteriosus, covering a range of topics such as gene functions, growth factors, transcription factors and cellular interactions, as well as stem cell engineering technologies. The book also presents recent advances in our understanding of the molecular mechanism of lung development, pulmonary hypertension and molecular regulation of the ductus arteriosus. As such, it is an ideal resource for physicians, scientists and investigators interested in the latest findings on the origins of congenital heart disease and potential future therapies involving pulmonary circulation/hypertension and the ductus arteriosus.
Book Synopsis Molecular Methods in Developmental Biology by : Matt Guille
Download or read book Molecular Methods in Developmental Biology written by Matt Guille and published by Springer Science & Business Media. This book was released on 2008-02-03 with total page 222 pages. Available in PDF, EPUB and Kindle. Book excerpt: The process whereby a single cell, the fertilized egg, develops into an adult has fascinated for centuries. Great progress in understanding that process, h- ever, has been made in the last two decades, when the techniques of molecular biology have become available to developmental biologists. By applying these techniques, the exact nature of many of the interactions responsible for forming the body pattern are now being revealed in detail. Such studies are a large, and it seems ever-expanding, part of most life-science groups. It is at newcomers to this field that this book is primarily aimed. A number of different plants and animals serve as common model org- isms for developmental studies. In Molecular Methods in Developmental Bi- ogy: Xenopus and Zebrafish, a range of the molecular methods applicable to two of these organisms are described, these are the South African clawed frog, Xenopus laevis, and the zebrafish, Brachydanio rerio. The embryos of both of these species develop rapidly and externally, making them particularly suited to investigations of early vertebrate development. However, both Xenopus and zebrafish have their own advantages and disadvantages. Xenopus have large, robust embryos that can be manipulated surgically with ease, but their pseudotetraploidy and long generation time make them unsuitable candidates for genetics. This disadvantage may soon be overcome by using the diploid Xenopus tropicalis, and early experiments are already underway. The transp- ent embryos of zebrafish render them well-suited for in situ hybridization and immunohistochemistry, and good for observing mutations in genetic screens.
Book Synopsis PanVascular Medicine by : Peter Lanzer
Download or read book PanVascular Medicine written by Peter Lanzer and published by Springer. This book was released on 2015-03-30 with total page 5004 pages. Available in PDF, EPUB and Kindle. Book excerpt: Vascular management and care has become a truly multidisciplinary enterprise as the number of specialists involved in the treatment of patients with vascular diseases has steadily increased. While in the past, treatments were delivered by individual specialists, in the twenty-first century a team approach is without doubt the most effective strategy. In order to promote professional excellence in this dynamic and rapidly evolving field, a shared knowledge base and interdisciplinary standards need to be established. Pan Vascular Medicine, 2nd edition has been designed to offer such an interdisciplinary platform, providing vascular specialists with state-of-the art descriptive and procedural knowledge. Basic science, diagnostics, and therapy are all comprehensively covered. In a series of succinct, clearly written chapters, renowned specialists introduce and comment on the current international guidelines and present up-to-date reviews of all aspects of vascular care.
Book Synopsis Molecular Mechanisms of Notch Signaling by : Tilman Borggrefe
Download or read book Molecular Mechanisms of Notch Signaling written by Tilman Borggrefe and published by Springer. This book was released on 2018-07-20 with total page 417 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book describes the Notch signaling pathway with a focus on molecular mechanisms. The Notch signaling pathway is a seemingly simple pathway that does not involve any second messenger. Upon ligand binding two consecutive proteolytic cleavages of the NOTCH receptor release the Notch intracellular domain from the membrane. The Notch intracellular domain migrates into the nucleus and activates gene expression. Recently, new technologies allowed us to better understand this pivotal signaling cascade and revealed new regulatory mechanisms. The different chapters cover many aspects of the Notch signaling focusing on the mechanisms governing the receptor/ligand interaction as well as on the downstream intracellular signaling events. Aspects of both canonical and non-canonical signaling are discussed and the function of Notch signaling in physiological and pathological contexts are elucidated. This book is not only intended for experts but it should also be a useful resource for young, sprouting scientists or interested scientists from other research areas, who may use this book as a stimulating starting point for further discoveries and developments.
Book Synopsis Microvascular Research: Biology and Pathology, Two-Volume Set by : David Shepro
Download or read book Microvascular Research: Biology and Pathology, Two-Volume Set written by David Shepro and published by Elsevier. This book was released on 2005-11-03 with total page 1353 pages. Available in PDF, EPUB and Kindle. Book excerpt: The microvasculature refers to the smallest blood vessels, arterial and venous, that nurture the tissues of each organ. Apart from transport, they also contribute to the systematic regulation of the body. In everyday terminology, the microcirculation is "where the action is." Microcirculation is directly involved in such disease states as Alzheimers, inflammation, tumor growth, diabetic retinopathy, and wound healing- plus cardiovascular fitness is directly related to the formation of new capillaries in large muscles. Microvascular Research is the first book devoted exclusively to this vital systemic component of the cardiovascular system and provides up to date mini-reviews of normal functions and clinical states. The contributing authors are senior scientists with international reputation in their given disciplines. This two-volume set is a broad, interdisciplinary work that encompasses basic research and clinical applications equally. * Broad coverage of both basic and clinical aspects of microvasculature research * Contains 167 chapters from over 300 international authors * Each chapter includes key figures and annotated references
Book Synopsis Fetal and Neonatal Lung Development by : Alan H. Jobe
Download or read book Fetal and Neonatal Lung Development written by Alan H. Jobe and published by Cambridge University Press. This book was released on 2016-04-18 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Lung disease affects more than 600 million people worldwide. While some of these lung diseases have an obvious developmental component, there is growing appreciation that processes and pathways critical for normal lung development are also important for postnatal tissue homeostasis and are dysregulated in lung disease. This book provides an authoritative review of fetal and neonatal lung development and is designed to provide a diverse group of scientists, spanning the basic to clinical research spectrum, with the latest developments on the cellular and molecular mechanisms of normal lung development and injury-repair processes, and how they are dysregulated in disease. The book covers genetics, omics, and systems biology as well as new imaging techniques that are transforming studies of lung development. The reader will learn where the field of lung development has been, where it is presently, and where it is going in order to improve outcomes for patients with common and rare lung diseases.
Book Synopsis Vascularization for Tissue Engineering and Regenerative Medicine by : Wolfgang Holnthoner
Download or read book Vascularization for Tissue Engineering and Regenerative Medicine written by Wolfgang Holnthoner and published by Springer. This book was released on 2021-06-09 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This reference work presents the basic principles of angiogenesis induction, including the roles of signaling factors such as hypoxia-inducible factors, biophysical stimulation and angiogenic cells. The book also covers lymphogenesis induction. Both the established fundamentals in the field as well as new trends in the vascularization of engineered tissues are discussed. These include pre-vascularization strategies using preparation of channeled scaffolds and preparation of decellularized blood vessel trees, approaches to inducing formation of microvasculature and approaches to inducing the growth of vascular networks. The authors expand on these concepts with current studies of dual-level approaches to engineer vascularized tissue composites. The book concludes with a discussion of current clinical approaches and the use of vascular grafts in the context of providing clinical practice with new tissue engineering strategies.
Book Synopsis Immune Regulation in Sepsis by : Yufeng Zhou
Download or read book Immune Regulation in Sepsis written by Yufeng Zhou and published by Frontiers Media SA. This book was released on 2023-10-30 with total page 159 pages. Available in PDF, EPUB and Kindle. Book excerpt:
