Tie1 regulates zebrafish cardiac morphogenesis through Tolloid-like 1 expression
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Tie1 regulates zebrafish cardiac morphogenesis through Tolloid-like 1 expression. / Carlantoni, Claudia; Allanki, Srinivas; Kontarakis, Zacharias; Rossi, Andrea; Piesker, Janett; Günther, Stefan; Stainier, Didier Y R.
In: DEV BIOL, Vol. 469, 01.01.2021, p. 54-67.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Tie1 regulates zebrafish cardiac morphogenesis through Tolloid-like 1 expression
AU - Carlantoni, Claudia
AU - Allanki, Srinivas
AU - Kontarakis, Zacharias
AU - Rossi, Andrea
AU - Piesker, Janett
AU - Günther, Stefan
AU - Stainier, Didier Y R
N1 - Copyright © 2020 Elsevier Inc. All rights reserved.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - 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.
AB - 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.
KW - Animals
KW - Animals, Genetically Modified
KW - Endothelial Cells/cytology
KW - Endothelium, Vascular/cytology
KW - Extracellular Matrix Proteins/genetics
KW - Gene Expression Regulation
KW - Heart/embryology
KW - Heart Defects, Congenital/genetics
KW - Morphogenesis
KW - Mutation
KW - Myocytes, Cardiac/cytology
KW - Receptor, TIE-1/genetics
KW - Tolloid-Like Metalloproteinases/genetics
KW - Transcriptome
KW - Zebrafish/embryology
KW - Zebrafish Proteins/genetics
U2 - 10.1016/j.ydbio.2020.09.008
DO - 10.1016/j.ydbio.2020.09.008
M3 - SCORING: Journal article
C2 - 32971120
VL - 469
SP - 54
EP - 67
JO - DEV BIOL
JF - DEV BIOL
SN - 0012-1606
ER -
