In:
Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 11 ( 2023-6-13)
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
2296-634X
DOI:
10.3389/fcell.2023.1169962
DOI:
10.3389/fcell.2023.1169962.s001
DOI:
10.3389/fcell.2023.1169962.s002
DOI:
10.3389/fcell.2023.1169962.s003
DOI:
10.3389/fcell.2023.1169962.s004
DOI:
10.3389/fcell.2023.1169962.s005
DOI:
10.3389/fcell.2023.1169962.s006
DOI:
10.3389/fcell.2023.1169962.s007
DOI:
10.3389/fcell.2023.1169962.s008
DOI:
10.3389/fcell.2023.1169962.s009
DOI:
10.3389/fcell.2023.1169962.s010
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2023
detail.hit.zdb_id:
2737824-X
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