scholarly journals Lamb1a regulates atrial growth by limiting second heart field addition during zebrafish heart development

Development ◽  
2021 ◽  
Author(s):  
Christopher J. Derrick ◽  
Eric J. G. Pollitt ◽  
Ashley Sanchez Sevilla Uruchurtu ◽  
Farah Hussein ◽  
Andrew J. Grierson ◽  
...  
Keyword(s):  
Heart Development ◽  
Cardiac Development ◽  
Cardiac Contractility ◽  
Asymmetric Structure ◽  
Specific Expression ◽  
Heart Morphogenesis ◽  
Second Heart Field ◽  
Heart Field ◽  
Heart Size ◽  
Zebrafish Heart

During early vertebrate heart development the heart transitions from a linear tube to a complex asymmetric structure, a morphogenetic process which occurs simultaneously with growth of the heart. Cardiac growth during early heart morphogenesis is driven by deployment of cells from the Second Heart Field (SHF) into both poles of the heart. Laminin is a core component of the extracellular matrix (ECM), and although mutations in laminin subunits are linked with cardiac abnormalities, no role for laminin has been identified in early vertebrate heart morphogenesis. We identified tissue-specific expression of laminin genes in the developing zebrafish heart, supporting a role for laminins in heart morphogenesis. Analysis of heart development in lamb1a zebrafish mutant embryos reveals mild morphogenetic defects and progressive cardiomegaly, and that Lamb1a functions to limit heart size during cardiac development by restricting SHF addition. lamb1a mutants exhibit hallmarks of altered haemodynamics, and blocking cardiac contractility in lamb1a mutants rescues heart size and atrial SHF addition. Together this suggests that laminin mediates interactions between SHF deployment and cardiac biomechanics during heart development and growth in the developing embryo.

scholarly journals Lamb1a regulates atrial growth by limiting excessive, contractility-dependent second heart field addition during zebrafish heart development

2021 ◽  
Author(s):  
Christopher J. Derrick ◽  
Eric J. G. Pollitt ◽  
Ashley Sanchez Sevilla Uruchurtu ◽  
Farah Hussein ◽  
Emily S. Noёl
Keyword(s):  
Heart Development ◽  
Cardiac Development ◽  
Basement Membranes ◽  
Atrioventricular Canal ◽  
Cardiac Morphogenesis ◽  
Heart Morphogenesis ◽  
Second Heart Field ◽  
Heart Field ◽  
Heart Size ◽  
Zebrafish Heart

AbstractDuring early vertebrate heart development, the heart transitions from a linear tube to a complex asymmetric structure. This process includes looping of the tube and ballooning of the emerging cardiac chambers, which occur simultaneously with growth of the heart. A key driver of cardiac growth is deployment of cells from the Second Heart Field (SHF) into both poles of the heart, with cardiac morphogenesis and growth intimately linked in heart development. Laminin is a core component of extracellular matrix (ECM) basement membranes, and although mutations in specific laminin subunits are linked with a variety of cardiac abnormalities, including congenital heart disease and dilated cardiomyopathy, no role for laminin has been identified in early vertebrate heart morphogenesis. We identified dynamic, tissue-specific expression of laminin subunit genes in the developing zebrafish heart, supporting a role for laminins in heart morphogenesis.lamb1amutants exhibit cardiomegaly from 2dpf onwards, with subsequent progressive defects in cardiac morphogenesis characterised by a failure of the chambers to compact around the developing atrioventricular canal. We show that loss oflamb1aresults in excess addition of SHF cells to the atrium, revealing that Lamb1a functions to limit heart size during cardiac development by restricting SHF addition to the venous pole.lamb1amutants exhibit hallmarks of altered haemodynamics, and specifically blocking cardiac contractility inlamb1amutants rescues heart size and atrial SHF addition. Furthermore, we identify that FGF and RA signalling, two conserved pathways promoting SHF addition, are regulated by heart contractility and are dysregulated inlamb1amutants, suggesting that laminin mediates interactions between SHF deployment, heart biomechanics, and biochemical signalling during heart development. Together, this describes the first requirement for laminins in early vertebrate heart morphogenesis, reinforcing the importance of specialised ECM composition in cardiac development.

Abstract MP245: Tet Proteins Regulate Second Heart Field Multipotent Progenitors Differentiating To Myocytes

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Shaohai Fang ◽  
Jia Li ◽  
Jeff D Steimle ◽  
Lei Guo ◽  
Yuhan Yang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Heart Development ◽  
Cardiac Development ◽  
Critical Role ◽  
Dna Demethylation ◽  
Lineage Specification ◽  
Second Heart Field ◽  
Heart Field ◽  
Cardiac Lineage ◽  
Tet Protein

DNA methylation and demethylation play an important role in shaping the epigenetic landscape and chromatin accessibility to control gene expression during development in mammals. Ten-eleven Translocation (Tet1, Tet2 and Tet3) is a family of dioxygenases that catalyze DNA methylation oxidation with ultimate DNA demethylation. Our previous study showed that cardiac-specific deletion of Tet2 and Tet3 could disrupt YY1-mediated long range chromatin interactions during heart development and lead to ventricular non-compaction cardiomyopathy. However, it is still unclear whether and how Tet protein mediated epigenetic modifications contribute to cardiac lineage specification during embryonic development. In this study, we generated cardiac specific Tet1-3 triple deficient (Tet-TKO) mouse lines using various cardiac specific Cres to evaluate the function of Tet protein in regulating cardiac lineage specification. We observed developmental defects at outflow tract (OFT) in Tet-TKO embryos, suggesting that Tet deficiency affects the second heart field (SHF) development. Single cell RNA-seq analysis further revealed the accumulation of multipotent SHF progenitors and subsequent halt of myocyte differentiation upon Tet depletion. At the molecular level, we found that Tet ablation perturbs the transcriptional network of Islet1, a transcription factor that is crucial for cardiac development in embryos. Overall, our study demonstrates a critical role of Tet-mediated epigenetic regulation for embryonic cardiac development.

scholarly journals Strong as a Hippo’s Heart: Biomechanical Hippo Signaling During Zebrafish Cardiac Development

2021 ◽  
Vol 9 ◽  
Author(s):  
Dorothee Bornhorst ◽  
Salim Abdelilah-Seyfried
Keyword(s):  
Heart Development ◽  
Cardiac Development ◽  
Hippo Pathway ◽  
Cardiac Progenitor Cells ◽  
Hippo Signaling ◽  
Cardiac Physiology ◽  
Heart Field ◽  
Dependent Growth ◽  
Secondary Heart Field ◽  
Zebrafish Heart

The heart is comprised of multiple tissues that contribute to its physiological functions. During development, the growth of myocardium and endocardium is coupled and morphogenetic processes within these separate tissue layers are integrated. Here, we discuss the roles of mechanosensitive Hippo signaling in growth and morphogenesis of the zebrafish heart. Hippo signaling is involved in defining numbers of cardiac progenitor cells derived from the secondary heart field, in restricting the growth of the epicardium, and in guiding trabeculation and outflow tract formation. Recent work also shows that myocardial chamber dimensions serve as a blueprint for Hippo signaling-dependent growth of the endocardium. Evidently, Hippo pathway components act at the crossroads of various signaling pathways involved in embryonic zebrafish heart development. Elucidating how biomechanical Hippo signaling guides heart morphogenesis has direct implications for our understanding of cardiac physiology and pathophysiology.

scholarly journals Temporally Distinct Six2 -Positive Second Heart Field Progenitors Regulate Mammalian Heart Development and Disease

Cell Reports ◽  
2017 ◽  
Vol 18 (4) ◽  
pp. 1019-1032 ◽  
Author(s):  
Zhengfang Zhou ◽  
Jingying Wang ◽  
Chaoshe Guo ◽  
Weiting Chang ◽  
Jian Zhuang ◽  
...  
Keyword(s):  
Heart Development ◽  
Second Heart Field ◽  
Mammalian Heart ◽  
Heart Field

The zebrafish as a model for cardiac development and regeneration

2018 ◽  
Author(s):  
Bill Chaudhry ◽  
José Luis de la Pompa ◽  
Nadia Mercader
Keyword(s):  
Heart Development ◽  
Cardiac Development ◽  
Model Organism ◽  
Laboratory Model ◽  
Developmental Studies ◽  
Sequencing Technologies ◽  
Technological Advances ◽  
The Common ◽  
Zebrafish Heart

The zebrafish has become an established laboratory model for developmental studies and is increasingly used to model aspects of human development and disease. However, reviewers and grant funding bodies continue to speculate on the utility of this Himalayan minnow. In this chapter we explain the similarities and differences between the heart from this distantly related vertebrate and the mammalian heart, in order to reveal the common fundamental processes and to prevent misleading extrapolations. We provide an overview of zebrafish including their husbandry, development, peculiarities of their genome, and technological advances, which make them a highly tractable laboratory model for heart development and disease. We discuss the controversies around morphants and mutants, and relate the development and structures of the zebrafish heart to mammalian counterparts. Finally, we give an overview of regeneration in the zebrafish heart and speculate on the role of the model organism in next-generation sequencing technologies.

scholarly journals Protein tyrosine phosphatase receptor zeta 1 deletion triggers defective heart morphogenesis in mice and zebrafish

2021 ◽  
Author(s):  
Stamatiki Katraki-Pavlou ◽  
Pinelopi Kastana ◽  
Dimitris Bousis ◽  
Despoina Ntenekou ◽  
Aimilia Varela ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Protein Tyrosine Phosphatase ◽  
Heart Development ◽  
Heart Function ◽  
Tyrosine Phosphatase ◽  
Embryonic Stem ◽  
Cell Types ◽  
Heart Morphogenesis ◽  
Protein Tyrosine ◽  
Zebrafish Heart

Protein tyrosine phosphatase receptor zeta 1 (PTPRZ1) is a transmembrane tyrosine phosphatase receptor highly expressed in embryonic stem cells. In the present work, gene expression analyses of Ptprz1-/- and Ptprz1+/+ mice endothelial cells and hearts pointed to an unidentified role of PTPRZ1 in heart development through regulation of heart-specific transcription factor genes. Echocardiography analysis in mice identified that both systolic and diastolic functions are affected in Ptprz1-/- compared to Ptprz1+/+ hearts, based on a dilated LV cavity, decreased ejection fraction and fraction shortening, and increased angiogenesis in Ptprz1-/- hearts, with no signs of cardiac hypertrophy. A zebrafish ptprz1-/- knockout was also generated and exhibits mis-regulated expression of developmental cardiac markers, bradycardia and defective heart morphogenesis characterized by enlarged ventricles and defected contractility. A selective PTPRZ1 tyrosine phosphatase inhibitor affected zebrafish heart development and function in a way like what is observed in the ptprz1-/- zebrafish. The same inhibitor had no effect in the function of the adult zebrafish heart, suggesting that PTPRZ1 is not important for the adult heart function, in line with data from the human cell atlas showing very low to negligible PTPRZ1 expression in the adult human heart. However, in line with the animal models, Ptprz1 was expressed in many different cell types in the human fetal heart, such as valvar, fibroblast-like, cardiomyocytes and endothelial cells. Collectively, these data suggest that PTPRZ1 regulates cardiac morphogenesis in a way that subsequently affects heart function and warrant further studies for the involvement of PTPRZ1 in idiopathic congenital cardiac pathologies.

scholarly journals Vangl2-Regulated Polarisation of Second Heart Field-Derived Cells Is Required for Outflow Tract Lengthening during Cardiac Development

PLoS Genetics ◽  
2014 ◽  
Vol 10 (12) ◽  
pp. e1004871 ◽  
Author(s):  
Simon A. Ramsbottom ◽  
Vipul Sharma ◽  
Hong Jun Rhee ◽  
Lorraine Eley ◽  
Helen M. Phillips ◽  
...  
Keyword(s):  
Cardiac Development ◽  
Outflow Tract ◽  
Second Heart Field ◽  
Heart Field

scholarly journals Isl1 Expression at the Venous Pole Identifies a Novel Role for the Second Heart Field in Cardiac Development

2007 ◽  
Vol 101 (10) ◽  
pp. 971-974 ◽  
Author(s):  
Brian S. Snarr ◽  
Jessica L. O’Neal ◽  
Mastan R. Chintalapudi ◽  
Elaine E. Wirrig ◽  
Aimee L. Phelps ◽  
...  
Keyword(s):  
Cardiac Development ◽  
Second Heart Field ◽  
Heart Field

scholarly journals A cis-regulatory-directed pipeline for the identification of genes involved in cardiac development and disease

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hieu T. Nim ◽  
Louis Dang ◽  
Harshini Thiyagarajah ◽  
Daniel Bakopoulos ◽  
Michael See ◽  
...  
Keyword(s):  
Heart Development ◽  
Congenital Heart ◽  
Cardiac Tissue ◽  
Cardiac Development ◽  
Heart Diseases ◽  
Regulatory Element ◽  
Adult Mortality ◽  
Disease Genes ◽  
Novel Genes ◽  
Specific Expression

Abstract Background Congenital heart diseases are the major cause of death in newborns, but the genetic etiology of this developmental disorder is not fully known. The conventional approach to identify the disease-causing genes focuses on screening genes that display heart-specific expression during development. However, this approach would have discounted genes that are expressed widely in other tissues but may play critical roles in heart development. Results We report an efficient pipeline of genome-wide gene discovery based on the identification of a cardiac-specific cis-regulatory element signature that points to candidate genes involved in heart development and congenital heart disease. With this pipeline, we retrieve 76% of the known cardiac developmental genes and predict 35 novel genes that previously had no known connectivity to heart development. Functional validation of these novel cardiac genes by RNAi-mediated knockdown of the conserved orthologs in Drosophila cardiac tissue reveals that disrupting the activity of 71% of these genes leads to adult mortality. Among these genes, RpL14, RpS24, and Rpn8 are associated with heart phenotypes. Conclusions Our pipeline has enabled the discovery of novel genes with roles in heart development. This workflow, which relies on screening for non-coding cis-regulatory signatures, is amenable for identifying developmental and disease genes for an organ without constraining to genes that are expressed exclusively in the organ of interest.

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