Wnt gradient formation: from source to sink

2006 ◽  
Vol 56 (4) ◽  
pp. 425-446 ◽  
Author(s):  
Hendrik Korswagen ◽  
Damien Coudreuse
Keyword(s):  
Concentration Gradient ◽  
Signalling Pathway ◽  
Current Understanding ◽  
Morphogenetic Field ◽  
Developmental Processes ◽  
Source To Sink ◽  
Gradient Formation ◽  
Wnt Ligands

AbstractThe secreted glycoproteins of the Wnt family activate a highly conserved signalling pathway that controls several developmental processes. Wnt ligands function as morphogens that act at a distance from their source by establishing a concentration gradient. The various fates of the Wnt responding cells along the morphogenetic field contribute to the precise patterning of the embryo and depend on the concentration of morphogen to which they are exposed. However, the different mechanisms that allow the controlled formation of the Wnt gradient are unclear. Here we give an overview of current understanding of the mechanisms that potentially control the spreading of the Drosophila Wnt ortholog Wingless.

Simple method for preparing a concentration gradient of serum components by freezing and thawing

1991 ◽  
Vol 37 (7) ◽  
pp. 1225-1229 ◽  
Author(s):  
Tetsuo Hirano ◽  
Toshiaki Yoneyama ◽  
Hiroko Matsuzaki ◽  
Takainitsu Sekine
Keyword(s):  
Concentration Gradient ◽  
Clinical Laboratory ◽  
Freezing Temperature ◽  
Test Results ◽  
Freezing And Thawing ◽  
Serum Samples ◽  
Simple Method ◽  
Gradient Formation ◽  
Repeated Freezing ◽  
Serum Components

Abstract We created a simple method for obtaining a series of successively more-concentrated samples from a serum without changing the ratio of its components. We froze a pooled serum and then allowed it to thaw undisturbed. The serum components formed a gradient of increasing concentration from the top of the sample to the bottom. We found that (a) in test results, each fraction of serum in the gradient showed almost the same relative concentrations of components (i.e., inorganic and organic compounds, proteins, metals, and hormones), irrespective of atomic or molecular mass; (b) the concentration gradient depended on the thawing temperature but not on the freezing temperature; (c) when we thawed the frozen sample with centrifugation, the slope of the concentration gradient increased with increasing centrifugal force; (d) when the thawed sample was fractionated into 10 fractions from the top to the bottom, the original serum concentration was always maintained between the sixth and seventh fractions from the top; and (e) the concentration gradient became steeper with repeated freezing and thawing. By using this method, one can easily prepare serum samples at gradients of concentration useful in the clinical laboratory, although the mechanism of gradient formation is still unclear.

The control of blood platelets by cAMP signalling

2014 ◽  
Vol 42 (2) ◽  
pp. 289-294 ◽  
Author(s):  
Zaher Raslan ◽  
Khalid M. Naseem
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Platelet Activation ◽  
Blood Platelets ◽  
Blood Platelet ◽  
Platelet Inhibition ◽  
Signalling Pathway ◽  
Current Understanding ◽  
Camp Signalling ◽  
Kinase A

Blood platelet activation must be tightly regulated to ensure a balance between haemostasis and thrombosis. The cAMP signalling pathway is the most powerful endogenous regulator of blood platelet activation. PKA (protein kinase A), the foremost effector of cAMP signalling in platelets, phosphorylates a number of proteins that are thought to modulate multiple aspects of platelet activation. In the present mini-review, we outline our current understanding of cAMP-mediated platelet inhibition and discuss some of the issues that require clarification.

PDE6 is an effector for the Wnt/Ca2+/cGMP-signalling pathway in development

2004 ◽  
Vol 32 (5) ◽  
pp. 792-796 ◽  
Author(s):  
H. Wang ◽  
Y. Lee ◽  
C.C. Malbon
Keyword(s):  
Enzyme Inhibitors ◽  
G Protein Coupled Receptors ◽  
Signalling Pathway ◽  
Two Dimensional ◽  
Direct Mapping ◽  
Cgmp Signalling ◽  
Cgmp Pathway ◽  
Wnt Ligands ◽  
Intracellular Concentrations ◽  
G Protein Coupled

Wnt signalling in development operates via members of the Frizzleds, G-protein-coupled receptors that bind specific Wnt ligands and mediate signalling via distinct pathways. The Wnt/Ca2+/cGMP pathway mediated by Frizzled-2 was discovered recently. Activation of this pathway leads to increased intracellular concentrations of Ca2+ and decreased intracellular concentrations of cGMP. The nature of the phosphodiesterase responsible for this Frizzled-2-mediated effect on cGMP levels was identified based on three separate criteria: (i) sensitivity to selective enzyme inhibitors, (ii) behaviour on chromatographic separation, and (ii) isolation by two-dimensional gels in tandem with direct mapping by MS of tryptic digests of the activity. On the basis of results from these three analyses, the cGMP-specific phosphodiesterase, PDE6, is demonstrated to be an effector for the Wnt/Ca2+/cGMP signalling pathway of development, which is mediated by Frizzled-2.

scholarly journals WNT4 secreted by tumor tissues promotes tumor progression in colorectal cancer by activation of the Wnt/β-catenin signalling pathway

2020 ◽  
Author(s):  
Dongmei Yang ◽  
Qing Li ◽  
Renduo Shang ◽  
Liwen Yao ◽  
Lianlian Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Resection ◽  
Signalling Pathway ◽  
Tumor Xenograft ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Normal Tissues ◽  
Potential Biomarker ◽  
Wnt Ligands

Abstract Background: Wingless and Int-related protein (Wnt) ligands are aberrantly expressed in patients with colorectal cancer (CRC). However, the aberrant level of Wnt ligands in serum have not been explored. Here, we aimed to identify the levels of WNT4 in serum and explored its oncogenic role in CRC Methods: The Oncomine database was used to analyze the relationship between WNT4 and the prognosis of CRC. ELISA was performed to measure WNT4 levels in serum and conditioned medium from fresh CRC tissues and adjacent normal tissues. Western blot and immunohistochemistry were carried out to measure the expression of WNT4 in human CRC tissues and adjacent normal tissues. The migration and invasion of CRC cells were determined by trans-well assay, and the effects of WNT4 on CRC invasion and metastasis in vivo were verified by tumor xenograft in nude mice. Cancer-associated fibroblasts (CAFs) and angiogenesis in subcutaneous nodules were detected by immunofluorescence (IF). In addition, the suspended spheres formation and tube formation assay were performed to explore the effects of WNT4 on CAFs and angiogenesis respectively. Results: WNT4 was significantly upregulated in serum of CRC patients, and CRC tissues were identified as an important source of elevated WNT4 levels in CRC patients. Interestingly, elevated levels of WNT4 in serum were downregulated after tumor resection. Furthermore, we found that WNT4 contributed to epithelial-to-mesenchymal transition (EMT) and activated fibroblasts by activating the WNT4/β-catenin pathway in vitro and in vivo. Moreover, angiogenesis was induced via the WNT4/β-catenin/Ang2 pathway. Those effects could be reversed by ICG-001, a β-catenin/TCF inhibitor. Conclusion: Our findings indicated that serum levels of WNT4 may be a potential biomarker for CRC. WNT4 secreted by colorectal cancer tissues promote the progression of CRC by inducing EMT, activate fibroblasts and promote angiogenesis through the canonical Wnt/β-catenin signalling pathway.

scholarly journals WNT4 secreted by tumor tissues promotes tumor progression in colorectal cancer by activation of the Wnt/β-catenin signalling pathway

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Dongmei Yang ◽  
Qing Li ◽  
Renduo Shang ◽  
Liwen Yao ◽  
Lianlian Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Resection ◽  
Signalling Pathway ◽  
Tumor Xenograft ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Normal Tissues ◽  
Potential Biomarker ◽  
Wnt Ligands

Abstract Background Wingless and Int-related protein (Wnt) ligands are aberrantly expressed in patients with colorectal cancer (CRC). However, the aberrant level of Wnt ligands in serum have not been explored. Here, we aimed to identify the levels of WNT4 in serum and explored its oncogenic role in CRC. Methods The Oncomine database was used to analyze the relationship between WNT4 and the prognosis of CRC. ELISA was performed to measure WNT4 levels in serum and conditioned medium from fresh CRC tissues and adjacent normal tissues. Western blot and immunohistochemistry were carried out to measure the expression of WNT4 in human CRC tissues and adjacent normal tissues. The migration and invasion of CRC cells were determined by trans-well assay, and the effects of WNT4 on CRC invasion and metastasis in vivo were verified by tumor xenograft in nude mice. Cancer-associated fibroblasts (CAFs) and angiogenesis in subcutaneous nodules were detected by immunofluorescence (IF). In addition, the suspended spheres formation and tube formation assay were performed to explore the effects of WNT4 on CAFs and angiogenesis respectively. Results WNT4 was significantly upregulated in serum of CRC patients, and CRC tissues were identified as an important source of elevated WNT4 levels in CRC patients. Interestingly, elevated levels of WNT4 in serum were downregulated after tumor resection. Furthermore, we found that WNT4 contributed to epithelial-to-mesenchymal transition (EMT) and activated fibroblasts by activating the WNT4/β-catenin pathway in vitro and in vivo. Moreover, angiogenesis was induced via the WNT4/β-catenin/Ang2 pathway. Those effects could be reversed by ICG-001, a β-catenin/TCF inhibitor. Conclusion Our findings indicated that serum levels of WNT4 may be a potential biomarker for CRC. WNT4 secreted by colorectal cancer tissues promote the progression of CRC by inducing EMT, activate fibroblasts and promote angiogenesis through the canonical Wnt/β-catenin signalling pathway.

scholarly journals Development of a Microfluidic Device to Form a Long Chemical Gradient in a Tissue from Both Ends with an Analysis of Its Appearance and Content

Micromachines ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1482
Author(s):  
Yasunori Tokuoka ◽  
Keiichi Kondo ◽  
Noboru Nakaigawa ◽  
Tadashi Ishida
Keyword(s):  
Concentration Gradient ◽  
Three Dimensional ◽  
Perfusion Culture ◽  
Longitudinal Direction ◽  
Tissue Specimen ◽  
Chemical Gradient ◽  
Metabolic Functions ◽  
Active Chemical ◽  
Gradient Formation ◽  
Blue Intensity

Tissue assays have improved our understanding of cancers in terms of the three-dimensional structures and cellular diversity of the tissue, although they are not yet well-developed. Perfusion culture and active chemical gradient formation in centimeter order are difficult in tissue assays, but they are important for simulating the metabolic functions of tissues. Using microfluidic technology, we developed an H-shaped channel device that could form a long concentration gradient of molecules in a tissue that we could then analyze based on its appearance and content. For demonstration, a cylindrical pork tissue specimen was punched and equipped in the H-shaped channel device, and both ends of the tissue were exposed to flowing distilled and blue-dyed water for 100 h. After perfusion, the tissue was removed from the H-shaped channel device and sectioned. The gradient of the blue intensity along the longitudinal direction of the tissue was measured based on its appearance and content. We confirmed that the measured gradients from the appearance and content were comparable.

scholarly journals Unanswered Questions Regarding Sex and BMP/TGF-β Signaling

2018 ◽  
Author(s):  
Tapan A. Shah ◽  
Melissa B. Rogers
Keyword(s):  
Signaling Pathways ◽  
Adult Life ◽  
Bmp Signaling ◽  
Current Understanding ◽  
Tgf Beta ◽  
Developmental Processes ◽  
Men And Women ◽  
Cardiovascular Pathologies

Crosstalk between the BMP and TGF-β signaling pathways regulates many complex developmental processes from the earliest stages of embryogenesis throughout adult life. In many situations, the two signaling pathways act reciprocally. For example, TGF-β signaling is generally pro-fibrotic whereas BMP signaling is anti-fibrotic and pro-calcific. Sex-specific differences occur in many diseases including cardiovascular pathologies. Differing ratios of fibrosis and calcification in stenotic valves suggests that BMP/TGF-β signaling may vary in men and women. In this review, we focus on the current understanding of the interplay between sex and BMP/TGF-β signaling and pose several unanswered questions.

scholarly journals Roles of Non-Canonical Wnt Signalling Pathways in Bone Biology

2021 ◽  
Vol 22 (19) ◽  
pp. 10840
Author(s):  
Jasna Lojk ◽  
Janja Marc
Keyword(s):  
Bone Tissue ◽  
Wnt Signalling ◽  
Signalling Pathway ◽  
Signalling Pathways ◽  
Bone Biology ◽  
Mineral Density ◽  
Wnt Signalling Pathway ◽  
Wnt Ligands ◽  
Canonical Wnt

The Wnt signalling pathway is one of the central signalling pathways in bone development, homeostasis and regulation of bone mineral density. It consists of numerous Wnt ligands, receptors and co-receptors, which ensure tight spatiotemporal regulation of Wnt signalling pathway activity and thus tight regulation of bone tissue homeostasis. This enables maintenance of optimal mineral density, tissue healing and adaptation to changes in bone loading. While the role of the canonical/β-catenin Wnt signalling pathway in bone homeostasis is relatively well researched, Wnt ligands can also activate several non-canonical, β-catenin independent signalling pathways with important effects on bone tissue. In this review, we will provide a thorough overview of the current knowledge on different non-canonical Wnt signalling pathways involved in bone biology, focusing especially on the pathways that affect bone cell differentiation, maturation and function, processes involved in bone tissue structure regulation. We will describe the role of the two most known non-canonical pathways (Wnt/planar cell polarity pathways and Wnt/Ca2+ pathway), as well as other signalling pathways with a strong role in bone biology that communicate with the Wnt signalling pathway through non-canonical Wnt signalling. Our goal is to bring additional attention to these still not well researched but important pathways in the regulation of bone biology in the hope of prompting additional research in the area of non-canonical Wnt signalling pathways.

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