Erschienen in:Frontiers in Cell and Developmental Biology
Sprache:
Nicht zu entscheiden
DOI:
10.3389/fcell.2023.1169962
ISSN:
2296-634X
Entstehung:
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Beschreibung:
<jats:p>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 <jats:italic>FIBRONECTIN 1</jats:italic> (<jats:italic>FN1</jats:italic>), the <jats:italic>VASCULAR CELL ADHESION MOLECULE 1</jats:italic> (<jats:italic>VCAM1</jats:italic>), as well as their receptor <jats:italic>INTEGRIN α4β1</jats:italic> (<jats:italic>ITGA4B1</jats:italic>) in HUVEC cells. Importantly, reducing the levels of <jats:italic>ITGA4, FN1</jats:italic>, and <jats:italic>VCAM1</jats:italic> 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.</jats:p>