A strategy to discover new organizers identifies a putative heart organizer

Anderson, Charles L.; Khan, Mohsin A.F.; Wong, Frances; Solovieva, Tatiana; Oliveira, Nidia M M; Baldock, Richard; Tickle, Cheryll; Burt, David W.; Stern, Claudio D.

doi:10.1038/ncomms12656

Cited by 34 publications

(34 citation statements)

References 81 publications

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“…Retinoic acid (RA) signaling from the lateral plate mesoderm has been shown to define the posterior identity of the heart tube [ 42 , 43 , 44 ]. In addition, the anterior intestinal portal endoderm, in addition to promoting the cardiac fate, can also pattern the heart tube by specifying ventricular and suppressing atrial identity [ 45 ]. All these observations are consistent with a model where a common population of cardiomyocytes may be patterned along the AP axis during the formation of the initial heart tube by extrinsic signals.…”

Section: Antero-posterior Patterning Of the Primitive Heart Tubementioning

confidence: 99%

Growth and Morphogenesis during Early Heart Development in Amniotes

Ivanovitch

Esteban

Torres

2017

JCDD

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In this review, we will focus on the growth and morphogenesis of the developing heart, an aspect of cardiovascular development to which Antoon Moorman and colleagues have extensively contributed. Over the last decades, genetic studies and characterization of regionally regulated gene programs have provided abundant novel insights into heart development essential to understand the basis of congenital heart disease. Heart morphogenesis, however, is inherently a complex and dynamic three-dimensional process and we are far from understanding its cellular basis. Here, we discuss recent advances in studying heart morphogenesis and regionalization under the light of the pioneering work of Moorman and colleagues, which allowed the reinterpretation of regional gene expression patterns under a new morphogenetic framework. Two aspects of early heart formation will be discussed in particular: (1) the initial formation of the heart tube and (2) the formation of the cardiac chambers by the ballooning process. Finally, we emphasize that in addition to analyses based on fixed samples, new approaches including clonal analysis, single-cell sequencing, live-imaging and quantitative analysis of the data generated will likely lead to novel insights in understanding early heart tube regionalization and morphogenesis in the near future.

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Section: Antero-posterior Patterning Of the Primitive Heart Tubementioning

confidence: 99%

Growth and Morphogenesis during Early Heart Development in Amniotes

Ivanovitch

Esteban

Torres

2017

JCDD

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“…Depending on the initial timing and site of ingression through the primitive streak, cardiac progenitors will be exposed to different signaling environments, which may influence their cardiac fate. BMPs and Fgfs secreted by the anterior endoderm (Alsan and Schultheiss, 2002;de Soysa et al, 2019;Lough and Sugi, 2000;Schultheiss et al, 1997), retinoic acid expressed in the posterior lateral plate mesoderm (Hochgreb et al, 2003;Xavier-Neto et al, 1999) and signals expressed in the anterior intestinal portal (AIP) at later stages (Anderson et al, 2016) all contribute to the patterning of the cardiac progenitors. A Hedgehog-Fgf signaling axis has also been recently proposed to pattern the anterior mesoderm to allocate the head and heart during mesodermal migration (Guzzetta et al, 2020).…”

Section: A Combination Of Intrinsic Factors and Inductive Events Specmentioning

confidence: 99%

Ventricular, atrial and outflow tract heart progenitors arise from spatially and molecularly distinct regions of the primitive streak

Ivanovitch

Soro-Barrio

Chakravarty

et al. 2020

Preprint

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The heart develops from two sources of mesoderm progenitors, the first and second heart field (FHF and SHF). Using a single-cell transcriptomic assay in combination with genetic lineage tracing, we find the FHF and SHF are subdivided into distinct pools of progenitors in gastrulating mouse embryos at earlier stages than previously thought. Each subpopulation has a distinct origin in the primitive streak. The first progenitors to leave the primitive streak contribute to the left ventricle, shortly after right ventricle progenitor emigrate, followed by the outflow tract and atrial progenitors. Although cells allocated to the outflow tract and atrium leave the primitive streak at a similar stage, they arise from different regions. Outflow tract originate from distal locations in the primitive streak while atrial progenitors are positioned more proximally. Moreover, single cell RNA sequencing demonstrates that the primitive streak cells contributing to the ventricles have a distinct molecular signature from those forming the outflow tract and atrium. We conclude that cardiac progenitors are pre-patterned within the primitive streak and this prefigures their allocation to distinct anatomical structures of the heart. Together, our data provide a new molecular and spatial map of mammalian cardiac progenitors that will support future studies of heart development, function and disease.

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“…The major drivers during heart embryogenesis were determined by principal component analysis (PCA) of microarray data from samples taken at different developmental stages [8,9]. Differential gene expression revealed by microarray data analysis was also used to prove that the anterior intestinal portal endoderm functions as a heart organizer, being capable to induce cardiac identity into noncardiac mesoderm even if heterotopically transplanted, and patterning cardiac tissue to express ventricular and suppress atrial region identifiers [36]. Moreover, single-cell RNA-seq was used to understand the earliest steps of cardiovascular lineage differentiation, analyzing MesP1-positive cardiovascular progenitor cells and different cardiac progenitor populations corresponding to the first and second heart fields at embryonic day E6.5 and E7.25, respectively, in mice [37,38].…”

Section: Discussionmentioning

confidence: 99%

Up-Down and Left-Right by the Heart Transcriptome

Iacobaş¹,

Amuzescu²,

Iacobaş³

2019

Preprint

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Myocardium transcriptomes of mouse left and right atria and ventricles were profiled separately to identify the differences that might be responsible for the distinct functional roles of the four heart chambers. In total, 16,886 distinct unigenes have been quantified in all 16 samples collected from four adult male mice from the same litter. 15.76% of the quantified genes on the left and 16.5% on the right exhibited differential expression between the corresponding atrium and ventricle of the same side, while 5.8% in atria and 1.2% in ventricles were differently expressed between the left and the right. Beyond the differentially expressed genes, the study revealed distinct expression control and coordination of ion channels and genes within the cardiac muscle contraction, oxidative phosphorylation, glycolysis/glucogenesis, calcium and adrenergic signaling pathways. Interestingly, while expression of Ank2 (encoding ankyrin-B) oscillates in phase with all its binding partners in the left ventricle, the percentage of synergistically expressed partners of Ank2 is 15% and 37% in the left and right atria and 74% in the right ventricle. The analysis revealed also the high interventricular synchrony of the expression of ion channels.

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A strategy to discover new organizers identifies a putative heart organizer

Cited by 34 publications

References 81 publications

Growth and Morphogenesis during Early Heart Development in Amniotes

Growth and Morphogenesis during Early Heart Development in Amniotes

Ventricular, atrial and outflow tract heart progenitors arise from spatially and molecularly distinct regions of the primitive streak

Up-Down and Left-Right by the Heart Transcriptome

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