PUBLICATION
Angiomotin regulates endothelial cell migration during embryonic angiogenesis
- Authors
- Aase, K., Ernkvist, M., Ebarasi, L., Jakobsson, L., Majumdar, A., Yi, C., Birot, O., Ming, Y., Kvanta, A., Edholm, D., Aspenström, P., Kissil, J., Claesson-Welsh, L., Shimono, A., and Holmgren, L.
- ID
- ZDB-PUB-070820-14
- Date
- 2007
- Source
- Genes & Development 21(16): 2055-2068 (Journal)
- Registered Authors
- Ebarasi, Lwaki, Majumdar, Arindam
- Keywords
- Angiostatin, neovascularization, embryogenesis, GTPase, chemotaxis, transgenic, zebrafish
- MeSH Terms
-
- Animals
- Base Sequence
- Body Patterning/genetics
- Body Patterning/physiology
- Cell Line
- Cell Movement/genetics
- Cell Movement/physiology
- DNA Primers/genetics
- Endothelial Cells/cytology
- Endothelial Cells/physiology
- Female
- Gene Deletion
- Gene Silencing
- Humans
- Intercellular Signaling Peptides and Proteins/deficiency
- Intercellular Signaling Peptides and Proteins/genetics
- Intercellular Signaling Peptides and Proteins/physiology*
- Membrane Proteins/deficiency
- Membrane Proteins/genetics
- Membrane Proteins/physiology*
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Microfilament Proteins/deficiency
- Microfilament Proteins/genetics
- Microfilament Proteins/physiology*
- Neovascularization, Physiologic/genetics
- Neovascularization, Physiologic/physiology*
- Phenotype
- Pregnancy
- Pseudopodia/ultrastructure
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/physiology*
- Zebrafish Proteins/deficiency
- Zebrafish Proteins/genetics
- Zebrafish Proteins/physiology*
- rac1 GTP-Binding Protein/metabolism
- PubMed
- 17699752 Full text @ Genes & Dev.
Citation
Aase, K., Ernkvist, M., Ebarasi, L., Jakobsson, L., Majumdar, A., Yi, C., Birot, O., Ming, Y., Kvanta, A., Edholm, D., Aspenström, P., Kissil, J., Claesson-Welsh, L., Shimono, A., and Holmgren, L. (2007) Angiomotin regulates endothelial cell migration during embryonic angiogenesis. Genes & Development. 21(16):2055-2068.
Abstract
The development of the embryonic vascular system into a highly ordered network requires precise control over the migration and branching of endothelial cells (ECs). We have previously identified angiomotin (Amot) as a receptor for the angiogenesis inhibitor angiostatin. Furthermore, DNA vaccination targeting Amot inhibits angiogenesis and tumor growth. However, little is known regarding the role of Amot in physiological angiogenesis. We therefore investigated the role of Amot in embryonic neovascularization during zebrafish and mouse embryogenesis. Here we report that knockdown of Amot in zebrafish reduced the number of filopodia of endothelial tip cells and severely impaired the migration of intersegmental vessels. We further show that 75% of Amot knockout mice die between embryonic day 11 (E11) and E11.5 and exhibit severe vascular insufficiency in the intersomitic region as well as dilated vessels in the brain. Furthermore, using ECs differentiated from embryonic stem (ES) cells, we demonstrate that Amot-deficient cells have intact response to vascular endothelial growth factor (VEGF) in regard to differentiation and proliferation. However, the chemotactic response to VEGF was abolished in Amot-deficient cells. We provide evidence that Amot is important for endothelial polarization during migration and that Amot controls Rac1 activity in endothelial and epithelial cells. Our data demonstrate a critical role for Amot during vascular patterning and endothelial polarization.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping