Svep1 is a binding ligand of Tie1 and affects specific aspects of facial lymphatic development in a Vegfc-independent manner

TY - JOUR

T1 - Svep1 is a binding ligand of Tie1 and affects specific aspects of facial lymphatic development in a Vegfc-independent manner

AU - Hußmann, Melina

AU - Schulte, Dörte

AU - Weischer, Sarah

AU - Carlantoni, Claudia

AU - Nakajima, Hiroyuki

AU - Mochizuki, Naoki

AU - Stainier, Didier Y R

AU - Zobel, Thomas

AU - Koch, Manuel

AU - Schulte-Merker, Stefan

N1 - © 2023, Hußmann et al.

PY - 2023/4/25

Y1 - 2023/4/25

N2 - 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.

AB - 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.

KW - Animals

KW - Humans

KW - Zebrafish/genetics

KW - Vascular Endothelial Growth Factor C/genetics

KW - Ligands

KW - Lymphatic Vessels/metabolism

KW - Lymphangiogenesis/genetics

KW - Receptor, TIE-2/genetics

KW - Cell Adhesion Molecules/metabolism

KW - Zebrafish Proteins/genetics

KW - Receptor, TIE-1/genetics

U2 - 10.7554/eLife.82969

DO - 10.7554/eLife.82969

M3 - SCORING: Journal article

C2 - 37097004

VL - 12

SP - e82969

JO - ELIFE

JF - ELIFE

SN - 2050-084X

ER -