scholarly journals Outflow Tract Formation—Embryonic Origins of Conotruncal Congenital Heart Disease

2021 ◽  
Vol 8 (4) ◽  
pp. 42
Author(s):  
Sonia Stefanovic ◽  
Heather C. Etchevers ◽  
Stéphane Zaffran
Keyword(s):  
Congenital Heart ◽  
Cardiac Development ◽  
Heart Defects ◽  
Dynamic Structure ◽  
Cell Types ◽  
Outflow Tract ◽  
Heart Tube ◽  
Heart Field ◽  
Multiple Cell ◽  
The Many

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.

Cardiac embryogenesis

ESC CardioMed ◽  
2018 ◽  
pp. 33-36
Author(s):  
Robert G. Kelly
Keyword(s):  
Progenitor Cells ◽  
Progenitor Cell ◽  
Congenital Heart ◽  
Heart Defects ◽  
Embryonic Heart ◽  
Heart Tube ◽  
Second Heart Field ◽  
Heart Field ◽  
Cell Niche ◽  
The Right

The embryonic heart forms in anterior lateral splanchnic mesoderm and is derived from Mesp1-expressing progenitor cells. During embryonic folding, the earliest differentiating progenitor cells form the linear heart tube in the ventral midline. The heart tube extends in length and loops to the right as new myocardium is progressively added at the venous and arterial poles from multipotent second heart field cardiovascular progenitor cells in contiguous pharyngeal mesoderm. While the linear heart tube gives rise to the left ventricle, the right ventricle, outflow tract, and a large part of atrial myocardium are derived from the second heart field. Progressive myocardial differentiation is controlled by intercellular signals within the progenitor cell niche. The embryonic heart is the template for septation and growth of the four-chambered definitive heart and defects in progenitor cell deployment result in a spectrum of common forms of congenital heart defects.

scholarly journals Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yonatan R. Lewis-Israeli ◽  
Aaron H. Wasserman ◽  
Mitchell A. Gabalski ◽  
Brett D. Volmert ◽  
Yixuan Ming ◽  
...  
Keyword(s):  
Congenital Heart Defects ◽  
Self Assembly ◽  
Human Heart ◽  
Congenital Heart ◽  
Cardiac Development ◽  
Heart Defects ◽  
Cell Types ◽  
Cellular Level ◽  
Cardiac Tissues

AbstractCongenital heart defects constitute the most common human birth defect, however understanding of how these disorders originate is limited by our ability to model the human heart accurately in vitro. Here we report a method to generate developmentally relevant human heart organoids by self-assembly using human pluripotent stem cells. Our procedure is fully defined, efficient, reproducible, and compatible with high-content approaches. Organoids are generated through a three-step Wnt signaling modulation strategy using chemical inhibitors and growth factors. Heart organoids are comparable to age-matched human fetal cardiac tissues at the transcriptomic, structural, and cellular level. They develop sophisticated internal chambers with well-organized multi-lineage cardiac cell types, recapitulate heart field formation and atrioventricular specification, develop a complex vasculature, and exhibit robust functional activity. We also show that our organoid platform can recreate complex metabolic disorders associated with congenital heart defects, as demonstrated by an in vitro model of pregestational diabetes-induced congenital heart defects.

scholarly journals Hippo-Yap Pathway Orchestrates Neural Crest Ontogenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaolei Zhao ◽  
Tram P. Le ◽  
Shannon Erhardt ◽  
Tina O. Findley ◽  
Jun Wang
Keyword(s):  
Cell Proliferation ◽  
Neural Crest ◽  
Congenital Heart ◽  
Heart Defects ◽  
Cell Types ◽  
Stem Cell Population ◽  
Significant Progress ◽  
Future Studies ◽  
Multiple Cell ◽  
Different Tissues

Neural crest (NC) cells are a migratory stem cell population in vertebrate embryogenesis that can give rise to multiple cell types, including osteoblasts, chondrocytes, smooth muscle cells, neurons, glia, and melanocytes, greatly contributing to the development of different tissues and organs. Defects in NC development are implicated in many human diseases, such as numerous syndromes, craniofacial aberration and congenital heart defects. Research on NC development has gained intense interest and made significant progress. Recent studies showed that the Hippo-Yap pathway, a conserved fundamental pathway with key roles in regulation of cell proliferation, survival, and differentiation, is indispensable for normal NC development. However, the roles and mechanisms of the Hippo-Yap pathway in NC development remain largely unknown. In this review, we summarize the key functions of the Hippo-Yap pathway indicated in NC induction, migration, proliferation, survival, and differentiation, as well as the diseases caused by its dysfunction in NC cells. We also discuss emerging current and future studies in the investigation of the Hippo-Yap pathway in NC development.

Cardiac embryogenesis

ESC CardioMed ◽  
2018 ◽  
pp. 33-36
Author(s):  
Robert G. Kelly
Keyword(s):  
Progenitor Cells ◽  
Progenitor Cell ◽  
Congenital Heart ◽  
Heart Defects ◽  
Embryonic Heart ◽  
Heart Tube ◽  
Second Heart Field ◽  
Heart Field ◽  
Cell Niche ◽  
The Right

The embryonic heart forms in anterior lateral splanchnic mesoderm and is derived from Mesp1-expressing progenitor cells. During embryonic folding, the earliest differentiating progenitor cells form the linear heart tube in the ventral midline. The heart tube extends in length and loops to the right as new myocardium is progressively added at the venous and arterial poles from multipotent second heart field cardiovascular progenitor cells in contiguous pharyngeal mesoderm. While the linear heart tube gives rise to the left ventricle, the right ventricle, outflow tract, and a large part of atrial myocardium are derived from the second heart field. Progressive myocardial differentiation is controlled by intercellular signals within the progenitor cell niche. The embryonic heart is the template for septation and growth of the four-chambered definitive heart and defects in progenitor cell deployment result in a spectrum of common forms of congenital heart defects.

scholarly journals Understanding Mechanisms of Chamber-Specific Differentiation Through Combination of Lineage Tracing and Single Cell Transcriptomics

2021 ◽  
Author(s):  
David M Gonzalez ◽  
Nadine Schrode ◽  
Tasneem Ebrahim ◽  
Kristin G Beaumont ◽  
Robert Sebra ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Single Cell ◽  
Cardiac Development ◽  
Cell Types ◽  
Myocardial Cell ◽  
Lineage Tracing ◽  
Metabolic Processes ◽  
Heart Tube ◽  
Heart Field ◽  
Bona Fide

The specification and differentiation of atrial and ventricular myocardial cell types during development is incompletely understood. We have previously shown that Foxa2 expression during gastrulation identifies a population of ventricular fated progenitors, allowing for labeling of these cells prior to the morphogenetic events that lead to chamber formation and acquisition of bona fide atrial or ventricular identity. In this study, we performed single cell RNA sequencing of Foxa2Cre;mTmG embryos at the cardiac crescent (E8.25), primitive heart tube (E8.75) and heart tube (E9.25) stage in order to understand the transcriptional mechanisms underlying formation of atrial and ventricular cell types at the earliest stages of cardiac development. We find that progression towards differentiated myocardial cell types occurs primarily based on heart field progenitor identity, and that different progenitor populations contribute to ventricular or atrial identity through separate differentiation mechanisms. We identified a number of candidate markers that define such differentiation processes, as well as differential regulation of metabolic processes that distinguish atrial and ventricular fated cells at the earliest stages of development. We further show that exogenous injection with retinoic acid during formation of the cardiac primordia causes defects in ventricular chamber size and is associated with dysregulation in FGF signaling in anterior second heart field cells and a shunt in differentiation towards orthogonal lineages. Retinoic acid also causes defects in cell-cycle exit in myocardial committed progenitors that result in formation of hypomorphic ventricles with decreased expression of important metabolic processes and sarcomere assembly. Collectively, our data identify, at a single cell level, distinct lineage trajectories during cardiac progenitor cell specification and differentiation, and the precise effects of manipulating cardiac progenitor field patterning via exogenous retinoic acid signaling.

scholarly journals Abnormal Cardiac Development in the Absence of Heart Glycogen

2004 ◽  
Vol 24 (16) ◽  
pp. 7179-7187 ◽  
Author(s):  
Bartholomew A. Pederson ◽  
Hanying Chen ◽  
Jill M. Schroeder ◽  
Weinian Shou ◽  
Anna A. DePaoli-Roach ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Cardiac Muscle ◽  
Heart Development ◽  
Congenital Heart ◽  
Cardiac Development ◽  
Glycogen Synthase ◽  
Heart Defects ◽  
Mendelian Inheritance ◽  
And Function ◽  
Impaired Cardiac Function

ABSTRACT Glycogen serves as a repository of glucose in many mammalian tissues. Mice lacking this glucose reserve in muscle, heart, and several other tissues were generated by disruption of the GYS1 gene, which encodes an isoform of glycogen synthase. Crossing mice heterozygous for the GYS1 disruption resulted in a significant underrepresentation of GYS1-null mice in the offspring. Timed matings established that Mendelian inheritance was followed for up to 18.5 days postcoitum (dpc) and that ∼90% of GYS1-null animals died soon after birth due to impaired cardiac function. Defects in cardiac development began between 11.5 and 14.5 dpc. At 18.5 dpc, the hearts were significantly smaller, with reduced ventricular chamber size and enlarged atria. Consistent with impaired cardiac function, edema, pooling of blood, and hemorrhagic liver were seen. Glycogen synthase and glycogen were undetectable in cardiac muscle and skeletal muscle from the surviving null mice, and the hearts showed normal morphology and function. Congenital heart disease is one of the most common birth defects in humans, at up to 1 in 50 live births. The results provide the first direct evidence that the ability to synthesize glycogen in cardiac muscle is critical for normal heart development and hence that its impairment could be a significant contributor to congenital heart defects.

scholarly journals Drosophila Heart as a Model for Cardiac Development and Diseases

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3078
Author(s):  
Anissa Souidi ◽  
Krzysztof Jagla
Keyword(s):  
Cardiac Dysfunction ◽  
Congenital Heart ◽  
Cardiac Development ◽  
Heart Diseases ◽  
Heart Defects ◽  
Fruit Fly ◽  
Model System ◽  
Fast Imaging

The Drosophila heart, also referred to as the dorsal vessel, pumps the insect blood, the hemolymph. The bilateral heart primordia develop from the most dorsally located mesodermal cells, migrate coordinately, and fuse to form the cardiac tube. Though much simpler, the fruit fly heart displays several developmental and functional similarities to the vertebrate heart and, as we discuss here, represents an attractive model system for dissecting mechanisms of cardiac aging and heart failure and identifying genes causing congenital heart diseases. Fast imaging technologies allow for the characterization of heartbeat parameters in the adult fly and there is growing evidence that cardiac dysfunction in human diseases could be reproduced and analyzed in Drosophila, as discussed here for heart defects associated with the myotonic dystrophy type 1. Overall, the power of genetics and unsuspected conservation of genes and pathways puts Drosophila at the heart of fundamental and applied cardiac research.

Development of the ventricles and valves

ESC CardioMed ◽  
2018 ◽  
pp. 44-49
Author(s):  
José M. Pérez-Pomares ◽  
José L. de la Pompa
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart ◽  
Cardiac Development ◽  
Experimental Studies ◽  
Heart Tube ◽  
Cellular Mechanisms ◽  
Valve Development ◽  
Tissue Interactions ◽  
The Right

The heart is the first functional organ of the vertebrate embryo, beginning to beat at around 4 weeks of gestation in humans. Tissue interactions orchestrate the complex patterning, proliferation, and differentiation processes that transform the embryonic cardiac primordium into the adult heart. During heart embryogenesis, cardiac mesoderm progenitor cells originate bilaterally during gastrulation and move rostrally to form the primitive heart tube, which will then loop towards the right and initiate septation to give rise to the mature four-chambered heart. Experimental studies in animal models have revealed the crucial role that a number of highly conserved signalling pathways, involving active molecular cross-talk between adjacent tissues, play in cardiac development, and how the alterations in these signalling mechanisms may cause congenital heart disease affecting the neonate or adult. Here, we describe briefly the knowledge gained on the molecular and cellular mechanisms underlying cardiac chamber and valve development and its implication in disease. This knowledge will ultimately facilitate the design of diagnostic and therapeutic strategies to treat congenital heart disease.

scholarly journals Right ventricular outflow tract reconstruction in adolescents and adults after previous repair of congenital heart defects

2012 ◽  
Vol 153 (31) ◽  
pp. 1219-1224 ◽  
Author(s):  
István Hartyánszky ◽  
László Székely ◽  
László Szudi ◽  
Sándor Mihályi ◽  
Krisztina Kádár ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Congenital Heart ◽  
Heart Defects ◽  
Right Ventricular Outflow Tract ◽  
Right Ventricular Dysfunction ◽  
Ventricular Outflow Tract ◽  
Pulmonary Valve Replacement ◽  
Outflow Tract ◽  
Adult Size ◽  
Adolescents And Adults

Due to successful surgical treatment of congenital heart defects in infants and children, the number of patients who reach the adolescent/adult age is continuously increasing. Aims: The authors sought to identify the short- and medium-term outcomes of reconstruction of right ventricular outflow tract in adolescents and adults who underwent surgical intervention for congenital heart defect in infancy or early childhood. Methods: Between 2001 and 2012, 48 patients (age: 15–39, mean 21 years) (30 tetralogy of Fallot, 11 pulmonary atresia + ventricular septal defect, 6 transposition of great arteries + ventricular septal defect + left ventricular outflow tract obstruction, and 1 truncus arteriosus) had repeat operation because of right ventricular dysfunction. All patients previously underwent right ventricular outflow tract procedures in early childhood. Results: In 31 patients, the small homograft, and in 9 patients the transannular-paths were replaced for “adult-size” homograft. Bioprosthetic pulmonary valve replacement was performed in pulmonary (6 patients) and homograft annuli (2 patients). In 14 patients, resection of the right ventricular outflow tract aneurism was also necessary to be performed. There was no early and mid-time (10 years) mortality. In 97.5% of patients with homograft-re-implantation, there was no need for repeat intervention for 5 years. Conclusions: The right ventricular outflow tract restoration in adolescents and adults is an effective procedure. The reconstruction should be performed in early adolescent period to prevent right ventricular dysfunction. The authors prefer using bioprosthetic pulmonary valve replacement in patients with adult-size pulmonary or homograft annulus. Orv. Hetil., 2012, 153, 1219–1224.

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