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Tie1 regulates zebrafish cardiac morphogenesis through Tolloid-like 1 expression.

Abstract：

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

journal_name

Dev Biol

journal_title

Developmental biology

authors

Carlantoni C,Allanki S,Kontarakis Z,Rossi A,Piesker J,Günther S,Stainier DYR

doi

10.1016/j.ydbio.2020.09.008

subject

Has Abstract

pub_date

2021-01-01 00:00:00

pages

54-67

eissn

0012-1606

issn

1095-564X

pii

S0012-1606(20)30256-6

journal_volume

469

pub_type

杂志文章

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