Tie1 regulates zebrafish cardiac morphogenesis through Tolloid-like 1 expression
| Autor: | Janett Piesker, Andrea Rossi, Didier Y.R. Stainier, Claudia Carlantoni, Srinivas Allanki, Stefan Günther, Zacharias Kontarakis |
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| Přispěvatelé: | University of Zurich, Stainier, Didier Y R |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Heart Defects
Congenital Tolloid-Like Metalloproteinases 610 Medicine & health 10071 Functional Genomics Center Zurich Receptor tyrosine kinase TIE1 Animals Genetically Modified Angiopoietin 1309 Developmental Biology 1307 Cell Biology 03 medical and health sciences Paracrine signalling 0302 clinical medicine Morphogenesis 1312 Molecular Biology Animals Myocytes Cardiac Sarcomere organization Molecular Biology Zebrafish 030304 developmental biology Extracellular Matrix Proteins 0303 health sciences Cardiac Jelly biology Endothelial Cells Heart Receptor TIE-1 Cell Biology Zebrafish Proteins biology.organism_classification Angiopoietin receptor Cell biology Gene Expression Regulation Mutation biology.protein 570 Life sciences Endothelium Vascular Transcriptome 030217 neurology & neurosurgery Developmental Biology |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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