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Angpt1 binding to Tie1 regulates the signaling required for lymphatic vessel development in zebrafish.
- Source :
-
Development (Cambridge, England) [Development] 2024 May 15; Vol. 151 (10). Date of Electronic Publication: 2024 May 28. - Publication Year :
- 2024
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Abstract
- Development of the vascular system is regulated by multiple signaling pathways mediated by receptor tyrosine kinases. 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 have revealed that the Tie2 locus has been lost in many vertebrate species, whereas 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, where Tie1 inhibits nuclear import of EGFP-Foxo1a. Angpt1/Tie1 signaling functions in endothelial cell migration and proliferation, and in lymphatic specification during early lymphangiogenesis, at least in part by modulating Vegfc/Vegfr3 signaling. Thus, we show that Angpt1/Tie1 signaling constitutes an essential signaling pathway for lymphatic development in zebrafish.<br />Competing Interests: Competing interests The authors declare no competing or financial interests.<br /> (© 2024. Published by The Company of Biologists Ltd.)
- Subjects :
- Animals
Cell Movement
Cell Proliferation
Endothelial Cells metabolism
Gene Expression Regulation, Developmental
Lymphatic Vessels metabolism
Lymphatic Vessels embryology
Mutation genetics
Protein Binding
Vascular Endothelial Growth Factor C metabolism
Vascular Endothelial Growth Factor C genetics
Vascular Endothelial Growth Factor Receptor-3 metabolism
Vascular Endothelial Growth Factor Receptor-3 genetics
Angiopoietin-1 metabolism
Angiopoietin-1 genetics
Lymphangiogenesis genetics
Receptor, TIE-1 metabolism
Receptor, TIE-1 genetics
Signal Transduction
Zebrafish embryology
Zebrafish metabolism
Zebrafish genetics
Zebrafish Proteins metabolism
Zebrafish Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9129
- Volume :
- 151
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Development (Cambridge, England)
- Publication Type :
- Academic Journal
- Accession number :
- 38742432
- Full Text :
- https://doi.org/10.1242/dev.202269