PUBLICATION
Angpt1 binding to Tie1 regulates the signaling required for lymphatic vessel development in zebrafish
- Authors
- Morooka, N., Gui, N., Ando, K., Sako, K., Fukumoto, M., Hasegawa, U., Hußmann, M., Schulte-Merker, S., Mochizuki, N., Nakajima, H.
- ID
- ZDB-PUB-240514-14
- Date
- 2024
- Source
- Development (Cambridge, England) 151(10): (Journal)
- Registered Authors
- Mochizuki, Naoki, Nakajima, Hiroyuki, Schulte-Merker, Stefan
- Keywords
- Live imaging, Lymphangiogenesis, Tie1, Zebrafish
- Datasets
- GEO:GSE240329
- MeSH Terms
-
- Angiopoietin-1*/genetics
- Angiopoietin-1*/metabolism
- Animals
- Cell Movement
- Cell Proliferation
- Endothelial Cells/metabolism
- Gene Expression Regulation, Developmental
- Lymphangiogenesis*/genetics
- Lymphatic Vessels*/embryology
- Lymphatic Vessels*/metabolism
- Mutation/genetics
- Protein Binding
- Receptor, TIE-1*/genetics
- Receptor, TIE-1*/metabolism
- Signal Transduction*
- Vascular Endothelial Growth Factor C/genetics
- Vascular Endothelial Growth Factor C/metabolism
- Vascular Endothelial Growth Factor Receptor-3/genetics
- Vascular Endothelial Growth Factor Receptor-3/metabolism
- Zebrafish*/embryology
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 38742432 Full text @ Development
Citation
Morooka, N., Gui, N., Ando, K., Sako, K., Fukumoto, M., Hasegawa, U., Hußmann, M., Schulte-Merker, S., Mochizuki, N., Nakajima, H. (2024) Angpt1 binding to Tie1 regulates the signaling required for lymphatic vessel development in zebrafish. Development (Cambridge, England). 151(10):.
Abstract
Development of the vascular system is regulated by multiple signaling pathways mediated by receptor tyrosine kinases (RTKs). Among them, angiopoietin (Ang)/Tie signaling regulates lymphatic and blood vessel development in mammals. Of the two Tie receptors, Tie2 is well known as a key mediator of Ang/Tie signaling, but unexpectedly, recent studies reveal that the Tie2 locus has been lost in many vertebrate species, while the Tie1 gene is more commonly present. However, Tie1-driven signaling pathways, including ligands and cellular functions, are not well understood. Here, we performed comprehensive mutant analyses of angiopoietins and Tie receptors in zebrafish and found that only angpt1 and tie1 mutants show defects in trunk lymphatic vessel development. Among zebrafish angiopoietins, only Angpt1 binds to Tie1 as a ligand. We indirectly monitored Ang1/Tie1 signaling and detected Tie1 activation in sprouting endothelial cells (ECs), where Tie1 inhibits nuclear import of EGFP-Foxo1a. Angpt1/Tie1 signaling functions in EC migration, proliferation, and lymphatic specification during early lymphangiogenesis, at least in part by modulating Vegfc/Vegfr3 signaling. Thus, we show Angpt1/Tie1 signaling to constitute an essential signaling pathway for lymphatic development in zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping