Svep1 is a binding ligand of Tie1 and affects specific aspects of facial lymphatic development in a Vegfc-independent manner
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Svep1 is a binding ligand of Tie1 and affects specific aspects of facial lymphatic development in a Vegfc-independent manner. / Hußmann, Melina; Schulte, Dörte; Weischer, Sarah; Carlantoni, Claudia; Nakajima, Hiroyuki; Mochizuki, Naoki; Stainier, Didier Y R; Zobel, Thomas; Koch, Manuel; Schulte-Merker, Stefan.
in: ELIFE, Jahrgang 12, 25.04.2023, S. e82969.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -