Correction to: Unveiling Complexity and Multipotentiality of Early Heart Fields

The heart is the first functioning organ to form during development. Similar to other organ primordia, the embryonic heart forms as a simple tube — in this case, a straight muscle-wrapped tube situated on the ventral side of the embryo. During gastrulation, the cardiac progenitors reside in the lateral plate mesoderm but maintain close contact with the underlying endoderm. In amniotes, these bilateral heart fields are initially organized as a pair of flat epithelia that move toward the embryonic midline and fuse above the anterior intestinal portal (AIP) to form the heart tube. This medial motion is typically attributed to active mesodermal migration over the underlying endoderm. In this view, the role of the endoderm is two-fold: to serve as a mechanically passive substrate for the crawling mesoderm and to secrete various growth factors necessary for cardiac specification and differentiation.

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The developmental origin of myocardium at the venous pole of the heart

10.1093/med/9780198757269.003.0008 ◽

2018 ◽

Author(s):

Bram van Wijk ◽

Phil Barnett ◽

Maurice J.B. van den Hoff

Keyword(s):

Developmental Changes ◽

Evolutionary Development ◽

Developmental Origin ◽

Two Component ◽

Heart Fields ◽

Large Vessels ◽

Mouse System

The focus of this chapter is an evaluation of the developmental origin of the myocardial component of the venous pole. The venous pole has a complex morphological architecture, reflecting its embryological and evolutionary development from several component parts. We describe the developmental changes observed in the architecture of the inflow of the heart and the large vessels that drain into the venous pole. As the formation of the proepicardium and the epicardial-derived cells are intimately connected to the forming inflow, this topic will also be covered. We compare the development of the inflow in chicken, mouse, and human. We then review the results obtained using the two-component genetic mouse system Cre-LoxP with respect to the myocardial components added to the forming cardiac inflow. These data are discussed within the now discriminated first, second, and third heart fields.

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Cardiac fields and myocardial cell lineages

10.1093/med/9780198757269.003.0004 ◽

2018 ◽

Author(s):

Christopher De Bono ◽

Magali Théveniau-Ruissy ◽

Robert G. Kelly

Keyword(s):

Myocardial Cell ◽

Early Embryo ◽

Lineage Tracing ◽

Genetic Lineage ◽

Field Development ◽

Cell Lineages ◽

Heart Field ◽

Experimental Approaches ◽

Genetic Lineage Tracing ◽

Heart Fields

We focus on the origin of myocardial cells in the first and second heart fields in splanchnic mesoderm in the early embryo. Genetic lineage tracing using Cre recombinase activated conditional reporter genes has made a major contribution to our understanding of cardiac progenitor cells and will be discussed together with other experimental approaches to analysing cell lineages at the clonal level. Interactions between myocardial, epicardial and endocardial lineages are essential for coordinated function and homeostasis of the normal heart. Perturbation of heart field development and myocardial lineage contributions to the heart through developmental or acquired pathologies results in and modulates the progression of cardiac disease. Understanding the origin of myocardial lineages during embryonic development and how they converge to generate an integrated heart is thus a major biomedical objective. Furthermore, reactivation of developmental programmes is likely to be of major importance in strategies aimed at repair of the damaged heart.

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Abstract 13269: Reduced Expression of scaRNAs Disrupts Spliceosome Function and Heart Development in Zebrafish and Infants with Tetralogy of Fallot

Circulation ◽

10.1161/circ.130.suppl_2.13269 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Douglas C Bittel ◽

Prakash Patil ◽

Tamayo Uechi ◽

Nataliya Kibiryeva ◽

Jennifer Marshall ◽

...

Keyword(s):

Tetralogy Of Fallot ◽

Heart Development ◽

Messenger Rna ◽

Dynamic Equilibrium ◽

Heart Defects ◽

Large Family ◽

New Paradigm ◽

Splice Isoforms ◽

The Right ◽

Heart Fields

The splicing of messenger RNA plays a fundamental role in regulating vertebrate development and differentiation. Although it is well established that alternative splicing (AS) plays an important role in regulating mammalian heart development, a clear link between misregulated splicing and congenital heart defects has not been shown. We recently reported that more than 50% of genes associated with heart development had significant changes in splice forms in the right ventricle of infants with tetralogy of Fallot (TOF; 14M/7F; all less than 1 yr old). Moreover, there was a significant decrease (30-50%, p<0.05) in the level of 12 scaRNAs. scaRNAs are members of the large family of noncoding small RNAs that are responsible for biochemical modification of specific nucleotides in spliceosomal and ribosomal RNAs. These 12 scaRNAs target two spliceosomal RNAs, U2 and U6. We used primary cells derived from the RV of infants with TOF to show a direct link between scaRNA levels and splice isoforms of several key genes regulating human heart development (e.g., GATA4, NOTCH2, DAAM1, DICER1, MBNL1 and 2). In addition, using available RNA-Seq data, we provide evidence that during zebrafish development, there are dynamic oscillations in scaRNAs and splice isoforms of genes that regulate heart development. We knocked down the expression of two scaRNAs; ACA35 (Scarna1) and U94 (Snord94), in zebrafish and saw a corresponding disruption of heart development. Importantly, there was an accompanying alteration in the ratios of splice isoforms of key cardiac regulatory genes. Based on these combined results, we propose that scaRNAs directly regulate the proficiency of the spliceosome by controlling spliceosomal RNA maturation. This in turn contributes to splice isoform dynamic equilibrium and ultimately heart development. These results are consistent with a failure of normal temporal and spatial splicing patterns during early embryonic development, leading to a breakdown in communication between the first and second heart fields, resulting in conotruncal misalignment and TOF. Our findings represent a new paradigm for understanding congenital cardiac malformations.

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Heart Fields and Cardiac Morphogenesis

Cold Spring Harbor Perspectives in Medicine ◽

10.1101/cshperspect.a015750 ◽

2014 ◽

Vol 4 (10) ◽

pp. a015750-a015750 ◽

Cited By ~ 92

Author(s):

R. G. Kelly ◽

M. E. Buckingham ◽

A. F. Moorman

Keyword(s):

Cardiac Morphogenesis ◽

Heart Fields

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Heart Fields: Spatial Polarity and Temporal Dynamics

The Anatomical Record ◽

10.1002/ar.22831 ◽

2013 ◽

Vol 297 (2) ◽

pp. 175-182 ◽

Cited By ~ 13

Author(s):

Radwan Abu-Issa

Keyword(s):

Temporal Dynamics ◽

Heart Fields

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Conotruncal myocardium arises from a secondary heart field

Development ◽

10.1242/dev.128.16.3179 ◽

2001 ◽

Vol 128 (16) ◽

pp. 3179-3188 ◽

Cited By ~ 18

Author(s):

Karen L. Waldo ◽

Donna H. Kumiski ◽

Kathleen T. Wallis ◽

Harriett A. Stadt ◽

Mary. R. Hutson ◽

...

Keyword(s):

Heart Development ◽

Outflow Tract ◽

Heart Tube ◽

In Ovo ◽

Atrioventricular Canal ◽

Lateral Plate ◽

Heart Field ◽

Dorsal Mesocardium ◽

Heart Fields ◽

Secondary Heart Field

The primary heart tube is an endocardial tube, ensheathed by myocardial cells, that develops from bilateral primary heart fields located in the lateral plate mesoderm. Earlier mapping studies of the heart fields performed in whole embryo cultures indicate that all of the myocardium of the developed heart originates from the primary heart fields. In contrast, marking experiments in ovo suggest that the atrioventricular canal, atria and conotruncus are added secondarily to the straight heart tube during looping. The results we present resolve this issue by showing that the heart tube elongates during looping, concomitant with accretion of new myocardium. The atria are added progressively from the caudal primary heart fields bilaterally, while the myocardium of the conotruncus is elongated from a midline secondary heart field of splanchnic mesoderm beneath the floor of the foregut. Cells in the secondary heart field express Nkx2.5 and Gata-4, as do the cells of the primary heart fields. Induction of myocardium appears to be unnecessary at the inflow pole, while it occurs at the outflow pole of the heart. Accretion of myocardium at the junction of the inflow myocardium with dorsal mesocardium is completed at stage 12 and later (stage 18) from the secondary heart field just caudal to the outflow tract. Induction of myocardium appears to move in a caudal direction as the outflow tract translocates caudally relative to the pharyngeal arches. As the cells in the secondary heart field begin to move into the outflow or inflow myocardium,they express HNK-1 initially and then MF-20, a marker for myosin heavy chain. FGF-8 and BMP-2 are present in the ventral pharynx and secondary heart field/outflow myocardium, respectively, and appear to effect induction of the cells in a manner that mimics induction of the primary myocardium from the primary heart fields. Neither FGF-8 nor BMP-2 is present as inflow myocardium is added from the primary heart fields. The addition of a secondary myocardium to the primary heart tube provides a new framework for understanding several null mutations in mice that cause defective heart development.

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Live imaging of heart tube development in mouse reveals alternating phases of cardiac differentiation and morphogenesis

10.1101/170522 ◽

2017 ◽

Cited By ~ 2

Author(s):

Kenzo Ivanovitch ◽

Susana Temiño ◽

Miguel Torres

Keyword(s):

Heart Development ◽

Initial Phase ◽

Tissue Level ◽

Mouse Embryos ◽

Cardiac Differentiation ◽

Second Phase ◽

Heart Tube ◽

Third Phase ◽

Heart Fields ◽

New Framework

ABSTRACTDuring vertebrate heart development two progenitor populations, first and second heart fields (FHF, SHF), sequentially contribute to longitudinal subdivisions of the heart tube (HT), with the FHF contributing the left ventricle and part of the atria, and the SHF the rest of the heart. Here we study the dynamics of cardiac differentiation and morphogenesis by tracking individual cells in live analysis of mouse embryos. We report that during an initial phase, FHF precursors differentiate rapidly to form a cardiac crescent, while limited morphogenesis takes place. In a second phase, no differentiation occurs while extensive morphogenesis, including splanchnic mesoderm sliding over the endoderm, results in HT formation. In a third phase, cardiac precursor differentiation resumes and contributes to SHF-derived regions and the dorsal closure of the HT. These results reveal tissue-level coordination between morphogenesis and differentiation during HT formation and provide a new framework to understand heart development.

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