197 research outputs found
Differentiation of the brain vasculature : the answer came blowing by the Wnt
No full textVascularization of the vertebrate brain takes place during embryonic development from a preformed perineural vascular plexus. As a consequence of the intimate contact with neuroectodermal cells the vessels, which are entering the brain exclusively via sprouting angiogenesis, acquire and maintain unique barrier properties known as the blood-brain barrier (BBB). The endothelial BBB depends upon the close association of endothelial cells with pericytes, astrocytes, neurons and microglia, which are summarized in the term neuro-vascular unit. Although it is known since decades that the CNS tissue provides the cues for BBB induction and differentiation in endothelial cells, the molecular mechanism remained obscure. Only recently, the canonical Wnt/beta-catenin pathway and the Wnt7a/7b growth factors have been implicated in brain angiogenesis on the one hand and in BBB induction on the other. This breakthrough in understanding the differentiation of the brain vasculature prompted us to review these findings embedded in the emerging concepts of Wnt signaling in the vasculature. In particular, interactions with other pathways that are crucial for vascular development such as VEGF, Notch, angiopoietins and Sonic hedgehog are discussed. Finally, we considered the potential role of the Wnt pathway in vascular brain pathologies in which BBB function is hampered, as for example in glioma, stroke and Alzheimer's disease
Ausspracherwerb junger Erwachsener - eine Frage der (Selbst)Steuerung?
No full textWild K. Ausspracherwerb junger Erwachsener - eine Frage der (Selbst)Steuerung? In: Ferraresi G, Liebner S, eds. SprachBrückenBauen. Materialien Deutsch als Fremdsprache. Vol 92. Göttingen: Universitätsverlag; 2014: 101-118
The multiple languages of endothelial cell-to-cell communication
No full textIntercellular adhesion plays a key role during development and maintenance of tissue homeostasis. Within the vascular system, cell-cell adhesion is particularly important for the correct formation, networking, and remodeling of vessels. Although in vascular endothelial cells adhesive junctions account for the integrity of the vessel wall, they are not to be considered as static molecular structures that function as intercellular glue. This becomes evident during the remodeling of the endothelium in various physiological and pathological processes, requiring highly dynamic vascular adhesion complexes. Moreover, it has recently become evident that, besides their structural functions, adhesion molecules involved in endothelial cell-cell interaction play an important role in inducing and integrating intracellular signals that, in turn, impact on several aspects of vascular cell physiology. In this review, we describe these recent findings focusing on junctional proteins at adherens and tight junctions. The role of this adhesion molecule-mediated signaling is discussed in the context of developmental and pathological angiogenesis
Ausspracheerwerb junger Erwachsener - eine Frage der (Selbst)Steuerung?
No full textWild K. Ausspracheerwerb junger Erwachsener - eine Frage der (Selbst)Steuerung? In: Ferraresi G, Liebner S, eds. SprachBrückenBauen. Materialien Deutsch als Fremdsprache. Vol Bd. 92. Göttingen: Universitätsverlag; 2014: 101-118
Endothelial cadherins and tumor angiogenesis
No full textAdherens junctions and more specifically cadherins play an important role in endothelial cell integrity and growth and, in general, in vascular morphogenesis. Besides their adhesive properties, cadherins may act by transferring intracellular signals through interaction with a complex network of cytoskeletal and signaling molecules. Cadherins may signal in different ways: through direct activation of signaling pathways, through interaction with cell-specific growth factor receptors or by controlling beta-catenin and/or other transcription factors' translocation to the nucleus. Endothelial cells present different cadherins which may transfer specific signals and exert distinct functional roles. VE-cadherin is endothelial-specific and the major constituent of adherens junctions. This protein is able to protect endothelial cells from apoptosis and contributes to contact inhibition of endothelial cell growth. N-cadherin is also abundantly expressed in the endothelium and may be important in modulating VE-cadherin expression. T cadherin, R-cadherin and VE-cadherin 2 were found in specific regions of the vascular tree but their role in vascular development or angiogenesis is still unclear. (c) 2005 Published by Elsevier Inc
Wnt activation of immortalized brain endothelial cells as a tool for generating a standardized model of the blood brain barrier in vitro
No full textReproducing the characteristics and the functional responses of the blood–brain barrier (BBB) in vitro represents an important task for the research community, and would be a critical biotechnological breakthrough. Pharmaceutical and biotechnology industries provide strong demand for inexpensive and easy-to-handle in vitro BBB models to screen novel drug candidates. Recently, it was shown that canonical Wnt signaling is responsible for the induction of the BBB properties in the neonatal brain microvasculature in vivo. In the present study, following on from earlier observations, we have developed a novel model of the BBB in vitro that may be suitable for large scale screening assays. This model is based on immortalized endothelial cell lines derived from murine and human brain, with no need for co-culture with astrocytes. To maintain the BBB endothelial cell properties, the cell lines are cultured in the presence of Wnt3a or drugs that stabilize β-catenin, or they are infected with a transcriptionally active form of β-catenin. Upon these treatments, the cell lines maintain expression of BBB-specific markers, which results in elevated transendothelial electrical resistance and reduced cell permeability. Importantly, these properties are retained for several passages in culture, and they can be reproduced and maintained in different laboratories over time. We conclude that the brain-derived endothelial cell lines that we have investigated gain their specialized characteristics upon activation of the canonical Wnt pathway. This model may be thus suitable to test the BBB permeability to chemicals or large molecular weight proteins, transmigration of inflammatory cells, treatments with cytokines, and genetic manipulation
Wnt/beta-catenin signaling controls development of the blood–brain barrier
No full textThe blood–brain barrier (BBB) is confined to the endothelium of brain capillaries and is indispensable for fluid homeostasis and neuronal function. In this study, we show that endothelial Wnt/beta-catenin (beta-cat) signaling regulates induction and maintenance of BBB characteristics during embryonic and postnatal development. Endothelial specific stabilization of beta-cat in vivo enhances barrier maturation, whereas inactivation of beta-cat causes significant down-regulation of claudin3 (Cldn3), up-regulation of plamalemma vesicle-associated protein, and BBB breakdown. Stabilization of beta-cat in primary brain endothelial cells (ECs) in vitro by N-terminal truncation or Wnt3a treatment increases Cldn3 expression, BBB-type tight junction formation, and a BBB characteristic gene signature. Loss of beta-cat or inhibition of its signaling abrogates this effect. Furthermore, stabilization of beta-cat also increased Cldn3 and barrier properties in nonbrain-derived ECs. These findings may open new therapeutic avenues to modulate endothelial barrier function and to limit the devastating effects of BBB breakdown
Alles unter DaF und Fach? Bestandsaufnahme, Handlungsbedarf und Vermittlungsansätze für Fachsprachenunterricht im internationalen Hochschulkontext
No full textGladitz A, Hunstiger A, Gültekin-Karakoç N, Zalipyatskikh N. Alles unter DaF und Fach? Bestandsaufnahme, Handlungsbedarf und Vermittlungsansätze für Fachsprachenunterricht im internationalen Hochschulkontext. In: Ferraresi G, Liebner S, eds. SprachBrückenBauen. 40. Jahrestagung des Fachverbandes Deutsch als Fremd- und Zweitsprache an der Universität Bamberg 2013. Materialien Deutsch als Fremdsprache. Vol 92. Göttingen: Universitätsverlag; 2015: 149-170
Beta-catenin is required for endothelial-mesenchymal transformation during heart cushion development in the mouse
No full textDuring heart development endocardial cells within the atrio-ventricular (AV) region undergo TGFbeta-dependent epithelial-mesenchymal transformation (EMT) and invade the underlying cardiac jelly. This process gives rise to the endocardial cushions from which AV valves and part of the septum originate. In this paper we show that in mouse embryos and in AV explants TGFbeta induction of endocardial EMT is strongly inhibited in mice deficient for endothelial beta-catenin, leading to a lack of heart cushion formation. Using a Wnt-signaling reporter mouse strain, we demonstrated in vivo and ex vivo that EMT in heart cushion is accompanied by activation of beta-catenin/TCF/Lef transcriptional activity. In cultured endothelial cells, TGFbeta2 induces alpha-smooth muscle actin (alphaSMA) expression. This process was strongly reduced in beta-catenin null cells, although TGFbeta2 induced smad phosphorylation was unchanged. These data demonstrate an involvement of beta-catenin/TCF/Lef transcriptional activity in heart cushion formation, and suggest an interaction between TGFbeta and Wnt-signaling pathways in the induction of endothelial-mesenchymal transformation
How do the environmental extremes of Siberian permafrost soils shape the composition of the bacterial soil community?
No full textMicrobial communities in permafrost soils of the Siberian Arctic are exposed to extreme environmental conditions. The soils are frozen throughout the entire year except for the short summer period, when thawing of the uppermost 20 to 50 cm of the permafrost sediment allows for the formation of a so-called active layer. Active layers show steep temperature gradients between 10 to 18 °C near the surface and 0 to 1 °C near the permafrost table. Additionally, seasonal freezing and thawing processes lead to the formation of patterns of low-centered polygons. Low-centered polygons determine a pronounced small-scale heterogeneity with regard to their physical and chemical properties between the elevated polygon rims and the depressed polygon centers.Within the active layer of a polygon rim, vertical profiles of potential methane oxidation rates in respond to different temperatures indicated a shift in the temperature optimum from 21 °C near the surface to 4 °C near the permafrost table [1]. This temperature shift could not be shown in samples of the polygon center. Based on these results we used 16S rDNA clone libraries as well as in-situ cell counting to compare the bacterial, in particular the methane oxidizing, community near the surface and near the permafrost table in samples of the polygon rim. The phylogenetic analyses show that the composition of the bacterial community near the surface is significantly different from the bacterial community near the permafrost table. The results also show that bacterial diversity and abundance in Siberian permafrost soils are comparably high as in temperate terrestrial environments.[1] Liebner. S. and Wagner, D. (in press) Abundance, distribution and potential activity of methane oxidizing bacteria in permafrost soils from the Lena Delta, Siberia. Environmental Microbiology doi: 10.1111/j.1462-2920.2006.01120.
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