heart tube
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2022 ◽  
Vol 73 ◽  
pp. 101896
Author(s):  
Paul Palmquist-Gomes ◽  
Sigolène M Meilhac

2021 ◽  
Vol 9 (1) ◽  
pp. 5
Author(s):  
Miquel Sendra ◽  
Jorge Domínguez ◽  
Miguel Torres ◽  
Oscar Ocaña

Early heart development depends on the coordinated participation of heterogeneous cellsources. As pioneer work from Adriana C. Gittenberger-de Groot demonstrated, characterizing thesedistinct cell sources helps us to understand congenital heart defects. Despite decades of researchon the segregation of lineages that form the primitive heart tube, we are far from understanding itsfull complexity. Currently, single-cell approaches are providing an unprecedented level of detail oncellular heterogeneity, offering new opportunities to decipher its functional role. In this review, wewill focus on three key aspects of early heart morphogenesis: First, the segregation of myocardial andendocardial lineages, which yields an early lineage diversification in cardiac development; second,the signaling cues driving differentiation in these progenitor cells; and third, the transcriptionalheterogeneity of cardiomyocyte progenitors of the primitive heart tube. Finally, we discuss howsingle-cell transcriptomics and epigenomics, together with live imaging and functional analyses, willlikely transform the way we delve into the complexity of cardiac development and its links withcongenital defects.


2021 ◽  
Author(s):  
Isaac Esteban ◽  
Patrick Schmidt ◽  
Susana Temino ◽  
Leif Kobbelt ◽  
Miguel Torres

Understanding organ morphogenesis requires a precise geometrical description of the tissues involved in the process. In highly regulative embryos, like those of mammals, morphological variability hinders the quantitative analysis of morphogenesis. In particular, the study of early heart development in mammals remains a challenging problem, due to imaging limitations and innate complexity. Around embryonic day 7.5 (E7.5), the cardiac crescent folds in an intricate and coordinated manner to produce a pumping linear heart tube at E8.25, followed by heart looping at E8.5. In this work we provide a complete morphological description of this process based on detailed imaging of a temporally dense collection of embryonic heart morphologies. We apply new approaches for morphometric staging and quantification of local morphological variations between specimens at the same stage. We identify hot spots of regionalized variability and identify left-right asymmetry in the inflow region starting at the late cardiac crescent stage, which represents the earliest signs of organ left-right asymmetry in the mammalian embryo. Finally, we generate a 3D+t digital model that provides a framework suitable for co-representation of data from different sources and for the computer modelling of the process.


2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Julie A Fischer ◽  
Megan Puckelwartz ◽  
Matthew Wolf ◽  
Mattia Quattrocelli ◽  
Lorenzo Pesce ◽  
...  

Background: Cardiomyopathy is a highly heritable disorder that carries a significant risk for heart failure and arrhythmias. Most inherited cardiomyopathies are characterized by variable penetrance and expressivity, which in part arises from additional genetic variation, known as genetic modifiers. Methods and Results: Genomic profiling of human cardiomyopathy cases identified enriched genetic variation in the gene MTCH2. Specifically, a truncating variant was found to be overrepresented in patients with cardiomyopathy compared to controls. MTCH2 encodes a mitochondrial carrier protein that has a role in regulating oxidative phosphorylation. To investigate fundamental mechanisms by which MTCH2 contributes to cardiac and metabolic phenotypes, we generated a knockdown model of the Drosophila MTCH2 ortholog, Mtch. We found that cardiac-specific Mtch reduction in flies produced heart tube dilation and reduced function as well as a shortened life span, documenting a clear role Mtch in the myocardium. Metabolomic profiling demonstrated cardiac deficiency of Mtch lowered the flux of glucose-derived metabolites to the citric acid cycle associated with reduced downstream oxygen consumption and ATP synthesis, causing an energy deficit. We generated a deletion of MTCH2 using gene editing in HEK293 cells. Similar to the fly model, these cells demonstrated reduced oxygen consumption in the presence of glucose, but not fatty acids, and had a higher level of inhibitory phosphorylation of pyruvate dehydrogenase, a critical regulator of glucose metabolism. These data suggest MTCH2 influences the efficiency of glucose oxidation and substrate usage, an important mode of cardiac energy generation, especially in the setting of heart failure. Conclusions: We identified MTCH2 as a modifier of the cardiomyopathy phenotype in humans. Reduction of MTCH2 resulted in impaired cardiac function with reduced oxygen consumption and increased glycolysis in a substrate dependent manner. Since failed hearts are more dependent on glycolysis, these data support that reduction of MTCH2 promotes heart failure and provides a mechanism by which MTCH2 acts as a deleterious genetic modifier in heart failure.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Estela Selma-Soriano ◽  
Carlos Casillas-Serra ◽  
Rubén Artero ◽  
Beatriz Llamusi ◽  
Juan Antonio Navarro ◽  
...  

AbstractHeart failure (HF) and the development of chronic kidney disease (CKD) have a direct association. Both can be cause and consequence of the other. Many factors are known, such as diabetes or hypertension, which can lead to the appearance and/or development of these two conditions. However, it is suspected that other factors, namely genetic ones, may explain the differences in the manifestation and progression of HF and CKD among patients. One candidate factor is Rph, a gene expressed in the nervous and excretory system in mammals and Drosophila, encoding a Rab small GTPase family effector protein implicated in vesicular trafficking. We found that Rph is expressed in the Drosophila heart, and the silencing of Rph gene expression in this organ had a strong impact in the organization of fibers and functional cardiac parameters. Specifically, we observed a significant increase in diastolic and systolic diameters of the heart tube, which is a phenotype that resembles dilated cardiomyopathy in humans. Importantly, we also show that silencing of Rabphilin (Rph) expression exclusively in the pericardial nephrocytes, which are part of the flies' excretory system, brings about a non-cell-autonomous effect on the Drosophila cardiac system. In summary, in this work, we demonstrate the importance of Rph in the fly cardiac system and how silencing Rph expression in nephrocytes affects the Drosophila cardiac system.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Federico Tessadori ◽  
Erika Tsingos ◽  
Enrico Sandro Colizzi ◽  
Fabian Kruse ◽  
Susanne C van den Brink ◽  
...  

Organ laterality refers to the left-right asymmetry in disposition and conformation of internal organs and is established during embryogenesis. The heart is the first organ to display visible left-right asymmetries through its left-sided positioning and rightward looping. Here, we present a new zebrafish loss-of-function allele for tbx5a, which displays defective rightward cardiac looping morphogenesis. By mapping individual cardiomyocyte behavior during cardiac looping, we establish that ventricular and atrial cardiomyocytes rearrange in distinct directions. As a consequence, the cardiac chambers twist around the atrioventricular canal resulting in torsion of the heart tube, which is compromised in tbx5a mutants. Pharmacological treatment and ex vivo culture establishes that the cardiac twisting depends on intrinsic mechanisms and is independent from cardiac growth. Furthermore, genetic experiments indicate that looping requires proper tissue patterning. We conclude that cardiac looping involves twisting of the chambers around the atrioventricular canal, which requires correct tissue patterning by Tbx5a.


2021 ◽  
Author(s):  
David M Gonzalez ◽  
Nadine Schrode ◽  
Tasneem Ebrahim ◽  
Kristin G Beaumont ◽  
Robert Sebra ◽  
...  

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.


Development ◽  
2021 ◽  
Author(s):  
Cristiana Dondi ◽  
Benjamin Bertin ◽  
Jean-Philippe Daponte ◽  
Inga Wojtowicz ◽  
Krzysztof Jagla ◽  
...  

The formation of the cardiac tube is a remarkable example of complex morphogenetic processes conserved from invertebrates to humans. It involves coordinated collective migration of contralateral rows of cardiac cells. The molecular processes underlying the specification of cardioblasts (CBs) prior to migration are well established and significant advances have been made in understanding the process of lumen formation. However, the mechanisms of collective cardiac cells migration remain elusive. Here we identified CAP and MSP300 as novel actors involved during CBs migration. They both exhibit highly similar temporal and spatial expression patterns in migrating cardiac cells and are necessary for the correct number and alignment of CBs, a prerequisite for the coordination of their collective migration. Our data suggest that CAP and MSP300 are part of a protein complex linking focal adhesion sites to nuclei via the actin cytoskeleton that maintains post-mitotic state and correct alignment of CBs.


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