2017
DOI: 10.1038/s41467-017-01950-1
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Opposite effects of Activin type 2 receptor ligands on cardiomyocyte proliferation during development and repair

Abstract: Zebrafish regenerate damaged myocardial tissue very effectively. Hence, insights into the molecular networks underlying zebrafish heart regeneration might help develop alternative strategies to restore human cardiac performance. While TGF-β signaling has been implicated in zebrafish cardiac regeneration, the role of its individual ligands remains unclear. Here, we report the opposing expression response during zebrafish heart regeneration of two genes, mstnb and inhbaa, which encode TGF-β family ligands. Using… Show more

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Cited by 65 publications
(74 citation statements)
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“…5I″-J″). These observations are in agreement with previous data showing that adult inhbaaoverexpressing fish exhibit hypertrabeculation but a grossly normal compact myocardial layer (Dogra et al, 2017). We conclude that inhbaa overexpression promotes proliferation specifically in the trabecular layer, but not in the compact layer, from early larval stages.…”
Section: The Tgfβ Pathway Ligand Inhbaa Promotes Trabecular Cardiomyosupporting
confidence: 93%
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“…5I″-J″). These observations are in agreement with previous data showing that adult inhbaaoverexpressing fish exhibit hypertrabeculation but a grossly normal compact myocardial layer (Dogra et al, 2017). We conclude that inhbaa overexpression promotes proliferation specifically in the trabecular layer, but not in the compact layer, from early larval stages.…”
Section: The Tgfβ Pathway Ligand Inhbaa Promotes Trabecular Cardiomyosupporting
confidence: 93%
“…We next checked cardiomyocyte proliferation in mstnb mutants, which display an increase in cardiomyocyte numbers in both compact and trabecular layers in adulthood (Dogra et al, 2017). Although the mutant larvae did not exhibit gross morphological phenotypes, we observed a slight increase in the number of EdU + cardiomyocytes, due to an increase in proliferation in both compact and trabecular layers ( Fig.…”
Section: The Tgfβ Pathway Ligand Inhbaa Promotes Trabecular Cardiomyomentioning
confidence: 90%
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“…Gene editing technologies like CRISPR/Cas9 have brought targeted mutagenesis to many species for traditionally rigorous genetic loss-of-function studies. Indeed, these approaches in making targeted mutations have uncovered requirements for Sox2, a SRY-related high-mobility group box transcription factor, connective tissue growth factor a (ctgfa) , a secreted matrix factor, and inhibin beta a a ( inhbaa ) in axolotl spinal cord regeneration, zebrafish spinal cord regeneration, and zebrafish heart regeneration, respectively (Dogra et al, 2017; Fei et al, 2014; Mokalled et al, 2016). Importantly, animal development was grossly normal in sox2, ctgfa , and inhbaa mutants, suggesting specific or preferential regenerative functions for these genes.…”
Section: Finding Triggers and Brakes For Regenerationmentioning
confidence: 99%
“…It is tempting to speculate that differences in the expression of these genes under oxygen stress, could contribute to the fibrotic heart phenotype observed in chimpanzees. Several of these genes have been implicated in heart physiology and disease suggesting that they could be relevant to the phenotype (Galvin et al 2000;Alfonso-Jaume et al 2006;Tseng et al 2009;Itoh et al 2016;Lu et al 2016;Dogra et al 2017). Many species-specific response genes are involved in post-transcriptional layers of the gene regulatory cascade including RNA modifications (METTL14), RNA folding (DDX20), splicing (CCDC49), nuclear-cytoplasmic transport (NUP214), and protein degradation (CBLL1, UBQLN4, TRIM13, DNAJB2).…”
Section: Inter-species Differences In Response To Oxygen Perturbationmentioning
confidence: 99%