PUBLICATION
Svep1 is a binding ligand of Tie1 and affects specific aspects of facial lymphatic development in a Vegfc-independent manner
- Authors
- Hußmann, M., Schulte, D., Weischer, S., Carlantoni, C., Nakajima, H., Mochizuki, N., Stainier, D.Y.R., Zobel, T., Koch, M., Schulte-Merker, S.
- ID
- ZDB-PUB-230426-50
- Date
- 2023
- Source
- eLIFE 12: (Journal)
- Registered Authors
- Mochizuki, Naoki, Nakajima, Hiroyuki, Schulte-Merker, Stefan, Stainier, Didier
- Keywords
- cell biology, cell migration, developmental biology, endothelial cells, lymphangiogenesis, zebrafish
- MeSH Terms
-
- Animals
- Cell Adhesion Molecules/metabolism
- Humans
- Ligands
- Lymphangiogenesis/genetics
- Lymphatic Vessels*/metabolism
- Receptor, TIE-1/genetics
- Receptor, TIE-1/metabolism
- Receptor, TIE-2/genetics
- Receptor, TIE-2/metabolism
- Vascular Endothelial Growth Factor C/genetics
- Vascular Endothelial Growth Factor C/metabolism
- Zebrafish*/genetics
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 37097004 Full text @ Elife
Citation
Hußmann, M., Schulte, D., Weischer, S., Carlantoni, C., Nakajima, H., Mochizuki, N., Stainier, D.Y.R., Zobel, T., Koch, M., Schulte-Merker, S. (2023) Svep1 is a binding ligand of Tie1 and affects specific aspects of facial lymphatic development in a Vegfc-independent manner. eLIFE. 12:.
Abstract
Multiple factors are required to form functional lymphatic vessels. Here, we uncover an essential role for the secreted protein Svep1 and the transmembrane receptor Tie1 during the development of subpopulations of the zebrafish facial lymphatic network. This specific aspect of the facial network forms independently of Vascular endothelial growth factor C (Vegfc) signalling, which otherwise is the most prominent signalling axis in all other lymphatic beds. Additionally, we find that multiple specific and newly uncovered phenotypic hallmarks of svep1 mutants are also present in tie1, but not in tie2 or vegfc mutants. These phenotypes are observed in the lymphatic vasculature of both head and trunk, as well as in the development of the dorsal longitudinal anastomotic vessel under reduced flow conditions. Therefore, our study demonstrates an important function for Tie1 signalling during lymphangiogenesis as well as blood vessel development in zebrafish. Furthermore, we show genetic interaction between svep1 and tie1 in vivo, during early steps of lymphangiogenesis, and demonstrate that zebrafish as well as human Svep1/SVEP1 protein bind to the respective Tie1/TIE1 receptors in vitro. Since compound heterozygous mutations for SVEP1 and TIE2 have recently been reported in human glaucoma patients, our data have clinical relevance in demonstrating a role for SVEP1 in TIE signalling in an in vivo setting.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping