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

TY - JOUR

T1 - Tek (Tie2) is not required for cardiovascular development in zebrafish

AU - Jiang, Zhen

AU - Carlantoni, Claudia

AU - Allanki, Srinivas

AU - Ebersberger, Ingo

AU - Stainier, Didier Y R

N1 - © 2020. Published by The Company of Biologists Ltd.

PY - 2020/10/12

Y1 - 2020/10/12

N2 - Angiopoietin/TIE signalling plays a major role in blood and lymphatic vessel development. In mouse, Tek (previously known as Tie2) mutants die prenatally due to a severely underdeveloped cardiovascular system. In contrast, in zebrafish, previous studies have reported that although embryos injected with tek morpholinos (MOs) exhibit severe vascular defects, tek mutants display no obvious vascular malformations. To further investigate the function of zebrafish Tek, we generated a panel of loss-of-function tek 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 tek mutants lacking the MO-binding site or the entire tek locus cause similar vascular defects to those observed in MO-injected +/+ siblings, indicating off-target effects of the MOs. Surprisingly, comprehensive phylogenetic profiling and synteny analyses reveal that Tek 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.

AB - Angiopoietin/TIE signalling plays a major role in blood and lymphatic vessel development. In mouse, Tek (previously known as Tie2) mutants die prenatally due to a severely underdeveloped cardiovascular system. In contrast, in zebrafish, previous studies have reported that although embryos injected with tek morpholinos (MOs) exhibit severe vascular defects, tek mutants display no obvious vascular malformations. To further investigate the function of zebrafish Tek, we generated a panel of loss-of-function tek 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 tek mutants lacking the MO-binding site or the entire tek locus cause similar vascular defects to those observed in MO-injected +/+ siblings, indicating off-target effects of the MOs. Surprisingly, comprehensive phylogenetic profiling and synteny analyses reveal that Tek 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.

KW - Animals

KW - Cardiovascular System/cytology

KW - Gene Editing

KW - Organogenesis/genetics

KW - Phylogeny

KW - Receptor, TIE-2/genetics

KW - Zebrafish

KW - Zebrafish Proteins/genetics

U2 - 10.1242/dev.193029

DO - 10.1242/dev.193029

M3 - SCORING: Journal article

C2 - 32928907

VL - 147

JO - DEVELOPMENT

JF - DEVELOPMENT

SN - 0950-1991

IS - 19

M1 - dev193029

ER -