scholarly journals Transient Nodal signalling in left precursors coordinates opposed asymmetries shaping the heart loop

2019 ◽  
Author(s):  
Audrey Desgrange ◽  
Jean-François Le Garrec ◽  
Ségolène Bernheim ◽  
Tobias Holm Bønnelykke ◽  
Sigolène M. Meilhac
Keyword(s):  
Congenital Heart ◽  
Morphological Changes ◽  
Heart Defects ◽  
Matrix Composition ◽  
Mouse Heart ◽  
Heart Tube ◽  
Random Generator ◽  
Downstream Effectors ◽  
Heart Looping ◽  
Insight Into

SummaryThe secreted factor Nodal has been shown to be a major left determinant. Although it is associated with severe congenital heart defects, its role in heart morphogenesis has remained poorly understood. Here, we report that Nodal is transiently active in precursors of the mouse heart tube poles, before the morphological changes of heart looping. In conditional mutants, we show that Nodal is not required to initiate asymmetric morphogenesis. We provide evidence of a heart-specific random generator of asymmetry that is independent of Nodal. Using 3D quantifications and simulations, we demonstrate that Nodal functions as a bias of this mechanism: it is required to amplify and coordinate opposed left-right asymmetries at the heart tube poles, thus generating a robust helical shape. We identify downstream effectors of Nodal signalling, regulating asymmetries in cell proliferation, cell differentiation and extra-cellular matrix composition. Our work provides novel insight into how Nodal regulates asymmetric organogenesis.

scholarly journals Embryonic Mouse Cardiodynamic OCT Imaging

2020 ◽  
Vol 7 (4) ◽  
pp. 42
Author(s):  
Andrew L. Lopez ◽  
Shang Wang ◽  
Irina V. Larina
Keyword(s):  
Blood Flow ◽  
Congenital Heart Defects ◽  
Heart Development ◽  
Congenital Heart ◽  
Cardiac Development ◽  
Heart Defects ◽  
Cellular Level ◽  
Mouse Heart ◽  
Embryonic Mouse ◽  
Insight Into

The embryonic heart is an active and developing organ. Genetic studies in mouse models have generated great insight into normal heart development and congenital heart defects, and suggest mechanical forces such as heart contraction and blood flow to be implicated in cardiogenesis and disease. To explore this relationship and investigate the interplay between biomechanical forces and cardiac development, live dynamic cardiac imaging is essential. Cardiodynamic imaging with optical coherence tomography (OCT) is proving to be a unique approach to functional analysis of the embryonic mouse heart. Its compatibility with live culture systems, reagent-free contrast, cellular level resolution, and millimeter scale imaging depth make it capable of imaging the heart volumetrically and providing spatially resolved information on heart wall dynamics and blood flow. Here, we review the progress made in mouse embryonic cardiodynamic imaging with OCT, highlighting leaps in technology to overcome limitations in resolution and acquisition speed. We describe state-of-the-art functional OCT methods such as Doppler OCT and OCT angiography for blood flow imaging and quantification in the beating heart. As OCT is a continuously developing technology, we provide insight into the future developments of this area, toward the investigation of normal cardiogenesis and congenital heart defects.

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.

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.

Ras-Related Signaling Pathways in Valve Development: Ebb and Flow

Physiology ◽  
2005 ◽  
Vol 20 (6) ◽  
pp. 390-397 ◽  
Author(s):  
Katherine E. Yutzey ◽  
Melissa Colbert ◽  
Jeffrey Robbins
Keyword(s):  
Signaling Pathways ◽  
Congenital Heart ◽  
Molecular Mechanisms ◽  
Heart Defects ◽  
Neurofibromatosis Type ◽  
Ras Signaling ◽  
Live Births ◽  
Valve Development ◽  
Insight Into

Congenital heart defects affect ~1 in every 100 live births, and deficits in the formation of the mitral, tricuspid, and outflow tract valves account for 20–25% of all cardiac malformations. Mutations in genes that affect Ras signaling have been identified in individuals with congenital valve disease associated with Noonan syndrome and neurofibromatosis type 1. Dissection of Ras-related signaling pathways during valvulogenesis provides seminal insight into cellular and molecular mechanisms that contribute to congenital heart disease.

Surface Strains in the Looping Embryonic Chick Heart Measured Using Optical Coherence Tomography

2007 ◽  
Author(s):  
Benjamen A. Filas ◽  
Larry A. Taber
Keyword(s):  
Heart Defects ◽  
Embryonic Chick ◽  
Heart Tube ◽  
Live Births ◽  
Shaped Tube ◽  
Vertebrate Embryo ◽  
Chick Heart ◽  
Embryonic Chick Heart ◽  
Left Right Asymmetry ◽  
Insight Into

The heart is the first functional organ in the vertebrate embryo. In the chick embryo, the heart begins beating at Hamburger and Hamilton [1] stage 10 (approximately 35 hours of a 21-day incubation period). The initially straight heart tube bends and twists into a c-shaped tube before reaching stage 12 (approximately 48 hours incubation). This process, known as c-looping, marks one of the first visible signs of left-right asymmetry in the embryo. Incorrect looping is one cause of congenital heart defects, where significant malformations occur in roughly 1% of human live births [2]. Understanding the mechanisms that drive c-looping could lend insight into the processes causing some of these defects.

scholarly journals Characterization of embryonic cardiac pacemaker and atrioventricular conduction physiology in Xenopus laevis using noninvasive imaging

2004 ◽  
Vol 286 (6) ◽  
pp. H2035-H2041 ◽  
Author(s):  
Heather L. Bartlett ◽  
Thomas D. Scholz ◽  
Fred S. Lamb ◽  
Daniel L. Weeks
Keyword(s):  
Xenopus Laevis ◽  
Congenital Heart ◽  
Morphological Changes ◽  
Heart Defects ◽  
Cardiac Pacemaker ◽  
Conduction System ◽  
Cardiac Conduction ◽  
Model Organisms ◽  
Morphological Evidence ◽  
Video Images

Congenital heart defects often include altered conduction as well as morphological changes. Model organisms, like the frog Xenopus laevis, offer practical advantages for the study of congenital heart disease. X. laevis embryos are easily obtained free living, and the developing heart is readily visualized. Functional and morphological evidence for a conduction system is available for adult frog hearts, but information on the normal properties of embryonic heart contraction is lacking, especially in intact animals. With the use of fine glass microelectrodes, we were able to obtain cardiac recordings and make standard electrophysiological measurements in 1-wk-old embryos ( stage 46). In addition, a system using digital analysis of video images was adapted for measurement of the standard cardiac intervals and compared with invasive measurements. Video images were obtained of the heart in live, pharmacologically paralyzed, stage 46 X. laevis embryos. Normal values for the timing of the cardiac cycle were established. Intervals determined by video analysis ( n = 53), including the atrial and ventricular cycle lengths (473 ± 10 ms and 464 ± 19 ms, respectively) and the atrioventricular interval (169 ± 5 ms) were not statistically different from those determined by intrathoracic cardiac recordings. We also present the data obtained from embryos treated with standard medications that affect the human conduction system. We conclude that the physiology of embryonic X. laevis cardiac conduction can be noninvasively studied by using digital video imaging. Additionally, we show the response of X. laevis embryonic hearts to chronotropic agents is similar but not identical to the response of the human heart.

scholarly journals A predictive model of asymmetric morphogenesis from 3D reconstructions of mouse heart looping dynamics

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Jean-François Le Garrec ◽  
Jorge N Domínguez ◽  
Audrey Desgrange ◽  
Kenzo D Ivanovitch ◽  
Etienne Raphaël ◽  
...  
Keyword(s):  
Predictive Model ◽  
Heart Defects ◽  
Cell Labelling ◽  
Mouse Heart ◽  
3D Reconstructions ◽  
Simple Description ◽  
Heart Looping ◽  
Dorsal Mesocardium ◽  
Shape Changes

How left-right patterning drives asymmetric morphogenesis is unclear. Here, we have quantified shape changes during mouse heart looping, from 3D reconstructions by HREM. In combination with cell labelling and computer simulations, we propose a novel model of heart looping. Buckling, when the cardiac tube grows between fixed poles, is modulated by the progressive breakdown of the dorsal mesocardium. We have identified sequential left-right asymmetries at the poles, which bias the buckling in opposite directions, thus leading to a helical shape. Our predictive model is useful to explore the parameter space generating shape variations. The role of the dorsal mesocardium was validated in Shh-/- mutants, which recapitulate heart shape changes expected from a persistent dorsal mesocardium. Our computer and quantitative tools provide novel insight into the mechanism of heart looping and the contribution of different factors, beyond the simple description of looping direction. This is relevant to congenital heart defects.

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