Tek (Tie2) is not required for cardiovascular development in zebrafish

Abstract

Angiopoietin/TIE signalling plays a major role in blood and lymphatic vessel development. In mouse, <i>Tek</i> (previously known as <i>Tie2</i>) mutants die prenatally due to a severely underdeveloped cardiovascular system. In contrast, in zebrafish, previous studies have reported that although embryos injected with <i>tek</i> morpholinos (MOs) exhibit severe vascular defects, <i>tek</i> mutants display no obvious vascular malformations. To further investigate the function of zebrafish Tek, we generated a panel of loss-of-function <i>tek</i> mutants, including RNA-less alleles, an allele lacking the MO-binding site, an in-frame deletion allele and a premature termination codon-containing allele. Our data show that all these mutants survive to adulthood with no obvious cardiovascular defects. MO injections into <i>tek</i> mutants lacking the MO-binding site or the entire <i>tek</i> locus cause similar vascular defects to those observed in MO-injected <i>+/+</i> siblings, indicating off-target effects of the MOs. Surprisingly, comprehensive phylogenetic profiling and synteny analyses reveal that <i>Tek</i> was lost in the largest teleost clade, suggesting a lineage-specific shift in the function of TEK during vertebrate evolution. Altogether, these data show that Tek is dispensable for zebrafish development, and probably dispensable in most teleost species.