TY  - JOUR
AU  - Hipke, Katrin
AU  - Pitter, Bettina
AU  - Hruscha, Alexander
AU  - van Bebber, Frauke
AU  - Modic, Miha
AU  - Bansal, Vikas
AU  - Lewandowski, Sebastian A
AU  - Orozco, Denise
AU  - Edbauer, Dieter
AU  - Bonn, Stefan
AU  - Haass, Christian
AU  - Pohl, Ulrich
AU  - Montanez, Eloi
AU  - Schmid, Bettina
TI  - Loss of TDP-43 causes ectopic endothelial sprouting and migration defects through increased fibronectin, vcam 1 and integrin α4/β1.
JO  - Frontiers in cell and developmental biology
VL  - 11
SN  - 2296-634X
CY  - Lausanne
PB  - Frontiers Media
M1  - DZNE-2023-00700
SP  - 1169962
PY  - 2023
AB  - 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.
KW  - ALS (Other)
KW  - TDP-43 (Other)
KW  - angiogenesis (Other)
KW  - neurodegeneration (Other)
KW  - zebrafish (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:37384248
C2  - pmc:PMC10299809
DO  - DOI:10.3389/fcell.2023.1169962
UR  - https://pub.dzne.de/record/258928
ER  -