%0 Journal Article
%A Hipke, Katrin
%A Pitter, Bettina
%A Hruscha, Alexander
%A van Bebber, Frauke
%A Modic, Miha
%A Bansal, Vikas
%A Lewandowski, Sebastian A
%A Orozco, Denise
%A Edbauer, Dieter
%A Bonn, Stefan
%A Haass, Christian
%A Pohl, Ulrich
%A Montanez, Eloi
%A Schmid, Bettina
%T Loss of TDP-43 causes ectopic endothelial sprouting and migration defects through increased fibronectin, vcam 1 and integrin α4/β1.
%J Frontiers in cell and developmental biology
%V 11
%@ 2296-634X
%C Lausanne
%I Frontiers Media
%M DZNE-2023-00700
%P 1169962
%D 2023
%X Aggregation 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.
%K ALS (Other)
%K TDP-43 (Other)
%K angiogenesis (Other)
%K neurodegeneration (Other)
%K zebrafish (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37384248
%2 pmc:PMC10299809
%R 10.3389/fcell.2023.1169962
%U https://pub.dzne.de/record/258928