PUBLICATION
Loss of TDP-43 causes ectopic endothelial sprouting and migration defects through increased fibronectin, vcam 1 and integrin α4/β1
- Authors
- Hipke, K., Pitter, B., Hruscha, A., van Bebber, F., Modic, M., Bansal, V., Lewandowski, S.A., Orozco, D., Edbauer, D., Bonn, S., Haass, C., Pohl, U., Montanez, E., Schmid, B.
- ID
- ZDB-PUB-230630-27
- Date
- 2023
- Source
- Frontiers in cell and developmental biology 11: 11699621169962 (Journal)
- Registered Authors
- Haass, Christian, Hruscha, Alexander, Schmid, Bettina, van Bebber, Frauke
- Keywords
- ALS, TDP-43, angiogenesis, neurodegeneration, zebrafish
- MeSH Terms
- none
- PubMed
- 37384248 Full text @ Front Cell Dev Biol
Citation
Hipke, K., Pitter, B., Hruscha, A., van Bebber, F., Modic, M., Bansal, V., Lewandowski, S.A., Orozco, D., Edbauer, D., Bonn, S., Haass, C., Pohl, U., Montanez, E., Schmid, B. (2023) Loss of TDP-43 causes ectopic endothelial sprouting and migration defects through increased fibronectin, vcam 1 and integrin α4/β1. Frontiers in cell and developmental biology. 11:11699621169962.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping