Hipke, KatrinPitter, BettinaHruscha, Alexandervan Bebber, FraukeModic, MihaBansal, VikasLewandowski, Sebastian A.Orozco, DeniseEdbauer, DieterBonn, StefanHaass, ChristianPohl, UlrichMontañez, EloiSchmid, Bettina2023-07-192023-07-192023-06-132296-634Xhttps://hdl.handle.net/2445/200880Aggregation 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.15 p.application/pdfengcc-by (c) Hipke, Katrin et al., 2023https://creativecommons.org/licenses/by/4.0/AngiogènesiMalalties neurodegenerativesPeix zebraProteïnesNeovascularizationNeurodegenerative DiseasesZebra danioProteinsinfo:eu-repo/semantics/article7378442023-07-19info:eu-repo/semantics/openAccess37384248