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000258928 1001_ $$0P:(DE-HGF)0$$aHipke, Katrin$$b0$$eFirst author
000258928 245__ $$aLoss of TDP-43 causes ectopic endothelial sprouting and migration defects through increased fibronectin, vcam 1 and integrin α4/β1.
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000258928 520__ $$aAggregation of the Tar DNA-binding protein of 43 kDa (TDP-43) is a pathological hallmark of amyotrophic lateral sclerosis and frontotemporal dementia and likely contributes to disease by loss of nuclear function. Analysis of TDP-43 function in knockout zebrafish identified an endothelial directional migration and hypersprouting phenotype during development prior lethality. In human umbilical vein cells (HUVEC) the loss of TDP-43 leads to hyperbranching. We identified elevated expression of FIBRONECTIN 1 (FN1), the VASCULAR CELL ADHESION MOLECULE 1 (VCAM1), as well as their receptor INTEGRIN α4β1 (ITGA4B1) in HUVEC cells. Importantly, reducing the levels of ITGA4, FN1, and VCAM1 homologues in the TDP-43 loss-of-function zebrafish rescues the angiogenic defects indicating the conservation of human and zebrafish TDP-43 function during angiogenesis. Our study identifies a novel pathway regulated by TDP-43 important for angiogenesis during development.
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000258928 650_7 $$2Other$$aALS
000258928 650_7 $$2Other$$aTDP-43
000258928 650_7 $$2Other$$aangiogenesis
000258928 650_7 $$2Other$$aneurodegeneration
000258928 650_7 $$2Other$$azebrafish
000258928 7001_ $$0P:(DE-HGF)0$$aPitter, Bettina$$b1
000258928 7001_ $$0P:(DE-2719)2009882$$aHruscha, Alexander$$b2
000258928 7001_ $$0P:(DE-2719)9000319$$avan Bebber, Frauke$$b3
000258928 7001_ $$aModic, Miha$$b4
000258928 7001_ $$0P:(DE-2719)2812055$$aBansal, Vikas$$b5
000258928 7001_ $$aLewandowski, Sebastian A$$b6
000258928 7001_ $$0P:(DE-2719)9000242$$aOrozco, Denise$$b7
000258928 7001_ $$0P:(DE-2719)2231621$$aEdbauer, Dieter$$b8
000258928 7001_ $$0P:(DE-HGF)0$$aBonn, Stefan$$b9
000258928 7001_ $$0P:(DE-2719)2202037$$aHaass, Christian$$b10
000258928 7001_ $$aPohl, Ulrich$$b11
000258928 7001_ $$aMontanez, Eloi$$b12
000258928 7001_ $$0P:(DE-2719)2241638$$aSchmid, Bettina$$b13$$eLast author
000258928 773__ $$0PERI:(DE-600)2737824-X$$a10.3389/fcell.2023.1169962$$gVol. 11, p. 1169962$$p1169962$$tFrontiers in cell and developmental biology$$v11$$x2296-634X$$y2023
000258928 8564_ $$uhttps://www.frontiersin.org/articles/10.3389/fcell.2023.1169962/full
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