scholarly journals Myocardial heterogeneity in permissiveness for epicardium-derived cells and endothelial precursor cells along the developing heart tube at the onset of coronary vascularization

Author(s):  
Heleen Lie-Venema ◽  
Ismail Eralp ◽  
Saskia Maas ◽  
Adriana C. Gittenberger-De Groot ◽  
Robert E. Poelmann ◽  
...  
Development ◽  
1993 ◽  
Vol 119 (2) ◽  
pp. 419-431 ◽  
Author(s):  
T.J. Lints ◽  
L.M. Parsons ◽  
L. Hartley ◽  
I. Lyons ◽  
R.P. Harvey

We have isolated two murine homeobox genes, Nkx-2.5 and Nkx-2.6, that are new members of a sp sub-family of homeobox genes related to Drosophila NK2, NK3 and NK4/msh-2. In this paper, we focus on the Nkx-2.5 gene and its expression pattern during post-implantation development. Nkx-2.5 transcripts are first detected at early headfold stages in myocardiogenic progenitor cells. Expression preceeds the onset of myogenic differentiation, and continues in cardiomyocytes of embryonic, foetal and adult hearts. Transcripts are also detected in future pharyngeal endoderm, the tissue believed to produce the heart inducer. Expression in endoderm is only found laterally, where it is in direct apposition to promyocardium, suggesting an interaction between the two tissues. After foregut closure, Nkx-2.5 expression in endoderm is limited to the pharyngeal floor, dorsal to the developing heart tube. The thyroid primordium, a derivative of the pharyngeal floor, continues to express Nkx-2.5 after transcript levels diminish in the rest of the pharynx. Nkx-2.5 transcripts are also detected in lingual muscle, spleen and stomach. The expression data implicate Nkx-2.5 in commitment to and/or differentiation of the myocardial lineage. The data further demonstrate that cardiogenic progenitors can be distinguished at a molecular level by late gastrulation. Nkx-2.5 expression will therefore be a valuable marker in the analysis of mesoderm development and an early entry point for dissection of the molecular basis of myogenesis in the heart.


2017 ◽  
Author(s):  
Natalie Gibb ◽  
Savo Lazic ◽  
Ashish R. Deshwar ◽  
Xuefei Yuan ◽  
Michael D. Wilson ◽  
...  

ABSTRACTA key event in vertebrate heart development is the timely addition of second heart field (SHF) progenitor cells to the poles of the heart tube. This accretion process must occur to the proper extent to prevent a spectrum of congenital heart defects (CHDs). However, the factors that regulate this critical process are poorly understood. Here we demonstrate that Hey2, a bHLH transcriptional repressor, restricts SHF progenitor accretion to the zebrafish heart. hey2 expression demarcated a distinct domain within the cardiac progenitor population. In the absence of Hey2 function an increase in myocardial cell number and SHF progenitors was observed. We found that Hey2 limited proliferation of SHF-derived cardiomyocytes in a cell-autonomous manner, prior to heart tube formation, and further restricted the developmental window over which SHF progenitors were deployed to the heart. Taken together, our data suggests a role for Hey2 in controlling the proliferative capacity and cardiac contribution of late-differentiating cardiac progenitors.


2008 ◽  
Vol 8 ◽  
pp. 194-211 ◽  
Author(s):  
Loretta L. Hoover ◽  
Elizabeth G. Burton ◽  
Bonnie A. Brooks ◽  
Steven W. Kubalak

The importance of retinoid signaling during cardiac development has long been appreciated, but recently has become a rapidly expanding field of research. Experiments performed over 50 years ago showed that too much or too little maternal intake of vitamin A proved detrimental for embryos, resulting in a cadre of predictable cardiac developmental defects. Germline and conditional knockout mice have revealed which molecular players in the vitamin A signaling cascade are potentially responsible for regulating specific developmental events, and many of these molecules have been temporally and spatially characterized. It is evident that intact and controlled retinoid signaling is necessary for each stage of cardiac development to proceed normally, including cardiac lineage determination, heart tube formation, looping, epicardium formation, ventricular maturation, chamber and outflow tract septation, and coronary arteriogenesis. This review summarizes many of the significant milestones in this field and particular attention is given to recently uncovered cross-talk between retinoid signaling and other developmentally significant pathways. It is our hope that this review of the role of retinoid signaling during formation, remodeling, and maturation of the developing heart will serve as a tool for future discoveries.


1999 ◽  
Vol 145 (5) ◽  
pp. 1063-1076 ◽  
Author(s):  
F. Frémion ◽  
M. Astier ◽  
S. Zaffran ◽  
A. Guillèn ◽  
V. Homburger ◽  
...  

The gene encoding the α subunit of the Drosophila Go protein is expressed early in embryogenesis in the precursor cells of the heart tube, of the visceral muscles, and of the nervous system. This early expression coincides with the onset of the mesenchymal-epithelial transition to which are subjected the cardial cells and the precursor cells of the visceral musculature. This gene constitutes an appropriate marker to follow this transition. In addition, a detailed analysis of its expression suggests that the cardioblasts originate from two subpopulations of cells in each parasegment of the dorsal mesoderm that might depend on the wingless and hedgehog signaling pathways for both their determination and specification. In the nervous system, the expression of Goα shortly precedes the beginning of axonogenesis. Mutants produced in the Goα gene harbor abnormalities in the three tissues in which the gene is expressed. In particular, the heart does not form properly and interruptions in the heart epithelium are repeatedly observed, henceforth the brokenheart (bkh) name. Furthermore, in the bkh mutant embryos, the epithelial polarity of cardial cells was not acquired (or maintained) in various places of the cardiac tube. We predict that bkh might be involved in vesicular traffic of membrane proteins that is responsible for the acquisition of polarity.


1992 ◽  
Vol 170 (1) ◽  
pp. 71-92 ◽  
Author(s):  
J. Jellies ◽  
D. M. Kopp ◽  
J. W. Bledsoe

The rhythmic pumping of the paired heart tubes in the medicinal leech Hirudo medicinalis offers an excellent system for studying the development of a simple behavior in terms of its neuronal and muscular components. The present experiments examined the development of identified heart excitor (HE) motor neurons during normal embryogenesis. Using intracellular impalements and dye-filling, we found that the HE motor neurons could be identified at an early stage of development and that they initially elaborated axonal arborizations in inappropriate target fields in the ventral body wall. These inappropriate projections were retracted as those at the appropriate target (developing heart tube muscle) extended. This remodelling occurred at least 4 days before the HEs acquired the adult phenotype of being driven to fire action potentials in a rhythmic pattern. Although the HEs exhibited centrally driven rhythmic oscillations late in embryogenesis, at earlier stages they exhibited largely a tonic discharge interrupted by bursts of inhibitory potentials in a periodic, but not a rhythmic, pattern. We also found what appeared to be non-rhythmic HE homologs in anterior and posterior segments where HE neurons have not been previously described. These homologs may project along similarly patterned guidance cues early in development, since they are at first indistinguishable from the definitive HEs, but they continued to elaborate both lateral and medial body wall projections over the same period that definitive HEs were expanding their arborizations over the developing heart tube and retracting their body wall projections. In both adult and embryonic leeches the homologs exhibited mostly tonic activity that was interrupted by pronounced, but non-rhythmic, hyperpolarizing postsynaptic potentials. Thus, there appears to be early segmental specification directing the final phenotype of the iterated neuron that, in most segments, becomes the HE motor neuron.


Development ◽  
1999 ◽  
Vol 126 (1) ◽  
pp. 75-84 ◽  
Author(s):  
C.L. Lien ◽  
C. Wu ◽  
B. Mercer ◽  
R. Webb ◽  
J.A. Richardson ◽  
...  

The homeobox gene Nkx2-5 is the earliest known marker of the cardiac lineage in vertebrate embryos. Nkx2-5 expression is first detected in mesodermal cells specified to form heart at embryonic day 7.5 in the mouse and expression is maintained throughout the developing and adult heart. In addition to the heart, Nkx2-5 is transiently expressed in the developing pharynx, thyroid and stomach. To investigate the mechanisms that initiate cardiac transcription during embryogenesis, we analyzed the Nkx2-5 upstream region for regulatory elements sufficient to direct expression of a lacZ transgene in the developing heart of transgenic mice. We describe a cardiac enhancer, located about 9 kilobases upstream of the Nkx2-5 gene, that fully recapitulates the expression pattern of the endogenous gene in cardiogenic precursor cells from the onset of cardiac lineage specification and throughout the linear and looping heart tube. Thereafter, as the atrial and ventricular chambers become demarcated, enhancer activity becomes restricted to the developing right ventricle. Transcription of Nkx2-5 in pharynx, thyroid and stomach is controlled by regulatory elements separable from the cardiac enhancer. This distal cardiac enhancer contains a high-affinity binding site for the cardiac-restricted zinc finger transcription factor GATA4 that is essential for transcriptional activity. These results reveal a novel GATA-dependent mechanism for activation of Nkx2-5 transcription in the developing heart and indicate that regulation of Nkx2-5 is controlled in a modular manner, with multiple regulatory regions responding to distinct transcriptional networks in different compartments of the developing heart.


Author(s):  
Maurice J. B. van den Hoff ◽  
Antoon F. M. Moorman

This chapter describes the formation of the adult four-chambered heart from the precardiac mesodermal cells. The precardiac mesoderm develops into a linear heart tube by the process of folding. The subsequent increase in size of the heart by the addition of precursor cells derived from the first and second heart fields is discussed. For the sake of clarity, the chapter describes the addition of precursor cells to the inflow and outflow, separately. Next, the formation of the ventricular chambers with respect to ballooning and differentiation into a compact and trabecular layer is discussed. Finally, the formation of the septa in the heart tube is described, creating the adult four-chambered heart.


Author(s):  
Hyeonyu Kim ◽  
Mingqiang Wang ◽  
David T. Paik

Vascular endothelial cells are a multifunctional cell type with organotypic specificity in their function and structure. In this review, we discuss various subpopulations of endothelial cells in the mammalian heart, which spatiotemporally regulate critical cellular and molecular processes of heart development via unique sets of angiocrine signaling pathways. In particular, elucidation of intercellular communication among the functional cell types in the developing heart has recently been accelerated by the use of single-cell sequencing. Specifically, we overview the heterogeneic nature of cardiac endothelial cells and their contribution to heart tube and chamber formation, myocardial trabeculation and compaction, and endocardial cushion and valve formation via angiocrine pathways.


eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Benoit G Bruneau

Within an embryo, a region next to the developing heart provides a niche where cardiac precursor cells can increase in number before they contribute to the development of this organ.


ESC CardioMed ◽  
2018 ◽  
pp. 39-44
Author(s):  
Maurice J. B. van den Hoff ◽  
Antoon F. M. Moorman

This chapter describes the formation of the adult four-chambered heart from the precardiac mesodermal cells. The precardiac mesoderm develops into a linear heart tube by the process of folding. The subsequent increase in size of the heart by the addition of precursor cells derived from the first and second heart fields is discussed. For the sake of clarity, the chapter describes the addition of precursor cells to the inflow and outflow, separately. Next, the formation of the ventricular chambers with respect to ballooning and differentiation into a compact and trabecular layer is discussed. Finally, the formation of the septa in the heart tube is described, creating the adult four-chambered heart.


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