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 ◽  
...  
2021 ◽  
Author(s):  
Christopher J. Derrick ◽  
Eric J. G. Pollitt ◽  
Ashley Sanchez Sevilla Uruchurtu ◽  
Farah Hussein ◽  
Emily S. Noёl

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.


PLoS Genetics ◽  
2014 ◽  
Vol 10 (12) ◽  
pp. e1004871 ◽  
Author(s):  
Simon A. Ramsbottom ◽  
Vipul Sharma ◽  
Hong Jun Rhee ◽  
Lorraine Eley ◽  
Helen M. Phillips ◽  
...  

Development ◽  
2021 ◽  
Author(s):  
Christopher J. Derrick ◽  
Eric J. G. Pollitt ◽  
Ashley Sanchez Sevilla Uruchurtu ◽  
Farah Hussein ◽  
Andrew J. Grierson ◽  
...  

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.


2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Shaohai Fang ◽  
Jia Li ◽  
Jeff D Steimle ◽  
Lei Guo ◽  
Yuhan Yang ◽  
...  

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.


Author(s):  
José Xavier-Neto ◽  
Sylvia Sura Trueba ◽  
Alberto Stolfi ◽  
Henrique Marques Souza ◽  
Tiago José Pascoal Sobreira ◽  
...  

2020 ◽  
Author(s):  
Fei Liang ◽  
Xiaoqing Zhang ◽  
Bo Wang ◽  
Juan Geng ◽  
Guoling You ◽  
...  

AbstractChromosome 4q deletion is one of the most frequently detected genomic imbalance events in congenital heart disease (CHD) patients. However, a portion of CHD-associated 4q deletions do not include known CHD genes. Alignment of those 4q deletions defined a minimal overlapping region including only one gene-SORBS2. Histological analysis of Sorbs2-/- heart revealed atrial septal hypoplasia/aplasia or double atrial septum. Mechanistically, SORBS2 had a dual role in maintaining sarcomeric integrity of cardiomyocytes and specifying the fate of second heart field (SHF) progenitors through c-ABL/NOTCH/SHH axis. In a targeted sequencing of a panel of known and candidate CHD genes on 300 CHD cases, we found that rare SORBS2 variants were significantly enriched in CHD patients. Our findings indicate that SORBS2 is a regulator of cardiac development and its haploinsufficiency may contribute to cardiac phenotype of 4q deletion syndrome. The presence of double atrial septum in Sorbs2-/- hearts reveals the first molecular etiology of this rare anomaly linked to paradoxical thromboembolism.


2020 ◽  
Vol 7 (4) ◽  
pp. 44
Author(s):  
Bjarke Jensen ◽  
Vincent M. Christoffels ◽  
Antoon F. M. Moorman

Robert H. Anderson is one of the most important and accomplished cardiac anatomists of the last decades, having made major contributions to our understanding of the anatomy of normal hearts and the pathologies of acquired and congenital heart diseases. While cardiac anatomy as a research discipline has become largely subservient to molecular biology, anatomists like Professor Anderson demonstrate anatomy has much to offer. Here, we provide cases of early anatomical insights on the heart that were rediscovered, and expanded on, by molecular techniques: migration of neural crest cells to the heart was deduced from histological observations (1908) and independently shown again with experimental interventions; pharyngeal mesoderm is added to the embryonic heart (1973) in what is now defined as the molecularly distinguishable second heart field; chambers develop from the heart tube as regional pouches in what is now considered the ballooning model by the molecular identification of regional differentiation and proliferation. The anatomical discovery of the conduction system by Purkinje, His, Tawara, Keith, and Flack is a special case because the main findings were never neglected in later molecular studies. Professor Anderson has successfully demonstrated that sound knowledge of anatomy is indispensable for proper understanding of cardiac development.


2021 ◽  
Vol 8 (4) ◽  
pp. 42
Author(s):  
Sonia Stefanovic ◽  
Heather C. Etchevers ◽  
Stéphane Zaffran

Anomalies in the cardiac outflow tract (OFT) are among the most frequent congenital heart defects (CHDs). During embryogenesis, the cardiac OFT is a dynamic structure at the arterial pole of the heart. Heart tube elongation occurs by addition of cells from pharyngeal, splanchnic mesoderm to both ends. These progenitor cells, termed the second heart field (SHF), were first identified twenty years ago as essential to the growth of the forming heart tube and major contributors to the OFT. Perturbation of SHF development results in common forms of CHDs, including anomalies of the great arteries. OFT development also depends on paracrine interactions between multiple cell types, including myocardial, endocardial and neural crest lineages. In this publication, dedicated to Professor Andriana Gittenberger-De Groot and her contributions to the field of cardiac development and CHDs, we review some of her pioneering studies of OFT development with particular interest in the diverse origins of the many cell types that contribute to the OFT. We also discuss the clinical implications of selected key findings for our understanding of the etiology of CHDs and particularly OFT malformations.


Development ◽  
2011 ◽  
Vol 138 (11) ◽  
pp. 2389-2398 ◽  
Author(s):  
D. Hami ◽  
A. C. Grimes ◽  
H.-J. Tsai ◽  
M. L. Kirby

2013 ◽  
Vol 112 (11) ◽  
pp. 1420-1432 ◽  
Author(s):  
Laura E. Briggs ◽  
Aimee L. Phelps ◽  
Elizabeth Brown ◽  
Jayant Kakarla ◽  
Robert H. Anderson ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document