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Tie1 regulates zebrafish cardiac morphogenesis through Tolloid-like 1 expression
Claudia Carlantoni1, Srinivas Allanki1, Zacharias Kontarakis1
1Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim, Germany.
Developmental Biology
|September 24, 2020
Summary
Tie1 receptor tyrosine kinase is crucial for zebrafish heart development. Its absence causes cardiac defects, but restoring Tolloid-like 1 (tll1) partially rescues these issues, highlighting a Tie1-tll1 signaling axis.
Area of Science:
- Cardiovascular Biology
- Developmental Biology
- Molecular Genetics
Background:
- Tie1 is a receptor tyrosine kinase in endothelial cells, modulating Angiopoietin/Tie2 signaling.
- Previous studies indicate Tie1's role in cardiovascular development, but its specific function during cardiac morphogenesis is less understood.
Purpose of the Study:
- To investigate the role of Tie1 in cardiac development using a zebrafish model.
- To elucidate the molecular mechanisms underlying Tie1-mediated cardiac development.
Main Methods:
- Generation and analysis of a zebrafish tie1 mutant line.
- Live imaging, ultrastructural analysis, and transcriptomic profiling of embryonic hearts.
- Rescue experiments involving mRNA injection to restore gene function.
Main Results:
- Homozygous tie1 mutant zebrafish embryos exhibit reduced endothelial/endocardial cell numbers, smaller heart size, increased cardiac jelly, and cardiomyocyte defects.
- Transcriptomic analysis revealed downregulation of Tolloid-like 1 (tll1) in tie1 mutants.
- Overexpression of tll1 partially rescued cardiac phenotypes in tie1 mutants.
Conclusions:
- The Tie1-Tolloid-like 1 (tll1) axis is critical for paracrine signaling during embryonic cardiac development.
- Tie1 signaling influences endothelial and myocardial cell populations and extracellular matrix organization.
- Zebrafish tie1 mutants provide a valuable model for studying cardiac development and related signaling pathways.
