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

Area of Science:

• Developmental Biology
• Vascular Biology
• Evolutionary Biology

Background:

• Angiopoietin/TIE signaling is crucial for blood and lymphatic vessel development.
• Mouse Tek (Tie2) mutants exhibit severe prenatal cardiovascular defects.
• Previous zebrafish studies showed conflicting results regarding Tek's role in vascular development.

Purpose of the Study:

• To investigate the function of zebrafish Tek (Tie2) in cardiovascular development.
• To clarify the discrepancies observed in previous zebrafish studies using morpholinos.
• To explore the evolutionary conservation of Tek's function in teleosts.

Main Methods:

• Generation and characterization of multiple zebrafish loss-of-function Tek mutants (RNA-less, MO-binding site deletion, in-frame deletion, PTC alleles).
• Assessment of cardiovascular and lymphatic system development in adult Tek mutants.
• Phylogenetic profiling and synteny analyses to investigate Tek evolution in teleosts.

Main Results:

• All generated zebrafish Tek mutants survived to adulthood without apparent cardiovascular defects.
• Morpholino injections in Tek mutant backgrounds mimicked defects seen in wild-type siblings, indicating off-target effects.
• Phylogenetic analyses revealed the loss of Tek in the largest teleost clade, suggesting lineage-specific functional shifts.

Conclusions:

• Zebrafish Tek (Tie2) is dispensable for cardiovascular development.
• Previous morpholino studies likely reported off-target effects, not true Tek function.
• Tek's dispensability in zebrafish suggests it may also be dispensable in many other teleost species due to evolutionary loss.