Tie1 regulates zebrafish cardiac morphogenesis through Tolloid-like 1 expression

Tie1 is a receptor tyrosine kinase expressed in endothelial cells, where it modulates Angiopoietin/Tie2 signaling. Previous studies have shown that mouse mutants exhibit severe cardiovascular defects; however, much remains to be learned about the role of Tie1, especially during cardiac development. To further understand function, we generated zebrafish tie1 mutant line. Homozygous embryos display reduced and endocardial cell numbers heart size. Live imaging ultrastructural analyses at embryonic stages revealed increased jelly thickness as well cardiomyocyte defects, including loss sarcomere organization altered shape. Transcriptomic profiling hearts uncovered downregulation tll1, which encodes Tolloid-like protease, tie1−/− compared with wild-type siblings. Using mRNA injections into one-cell stage embryos, found tll1 overexpression could partially rescue phenotypes myocardial thickness. Altogether, our results indicate importance Tie1-Tolloid-like 1 axis paracrine signaling