scholarly journals Endoderm Nitric Oxide Signals to Regulate Nascent Development of Cardiac Progenitors in Chicken Embryos

2020 ◽  
Author(s):  
Devan H. Shah ◽  
Sujoy K. Biswas ◽  
Adrian M. Martin ◽  
Simone Bianco ◽  
Wilfred F. Denetclaw
Keyword(s):  
Nitric Oxide ◽  
Heart Development ◽  
Tube Formation ◽  
Heart Tube ◽  
Signal Molecule ◽  
Cardiac Progenitors ◽  
Field Development ◽  
Physiological Signal ◽  
No Signaling ◽  
Differentiation And Proliferation

AbstractHeart development in the chicken embryo is regulated by a concert of cardiogenic morphogens and signaling molecules, but the physiological signal molecule nitric oxide(NO) has not been studied in the context of heart formation. A dynamic investigation of endoderm NO formation demonstrates for the first time a correlation with the established development events of the cardiac heart fields and heart tube. Manipulation of endoderm NO signaling demonstrate a role of NO signaling in the differentiation and proliferation of cardiac progenitors for heart tube formation and cardiac heart field development. To investigate NO in the proliferation of myocardial cells in the heart tube embryos, a computer vision based artificial intelligence approach is followed to automate the long and tedious job of counting cells in a large image dataset. We document NO as an important signaling molecule in the regulation of nascent embryonic cardiogenesis whose effects on other early cardiogenic morphogens is unknown.

scholarly journals Hey2 restricts cardiac progenitor addition to the developing heart

2017 ◽  
Author(s):  
Natalie Gibb ◽  
Savo Lazic ◽  
Ashish R. Deshwar ◽  
Xuefei Yuan ◽  
Michael D. Wilson ◽  
...  
Keyword(s):  
Heart Development ◽  
Heart Defects ◽  
Myocardial Cell ◽  
Cell Number ◽  
Tube Formation ◽  
Heart Tube ◽  
Cardiac Progenitors ◽  
Developing Heart ◽  
Heart Field ◽  
A Cell

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.

scholarly journals The Expanding Role for Retinoid Signaling in Heart Development

2008 ◽  
Vol 8 ◽  
pp. 194-211 ◽  
Author(s):  
Loretta L. Hoover ◽  
Elizabeth G. Burton ◽  
Bonnie A. Brooks ◽  
Steven W. Kubalak
Keyword(s):  
Vitamin A ◽  
Heart Development ◽  
Cardiac Development ◽  
Tube Formation ◽  
Conditional Knockout ◽  
Heart Tube ◽  
Developmental Defects ◽  
Retinoid Signaling ◽  
Developing Heart ◽  
Cardiac Lineage

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.

Abstract 16013: Direct Nkx2-5 Transcriptional Repression of Isl1 Controls Cardiomyocyte Subtype Identity

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Alexander Goedel ◽  
Tatjana Dorn ◽  
Jason T Lam ◽  
Franziska Herrmann ◽  
Jessica Haas ◽  
...  
Keyword(s):  
Heart Development ◽  
Transcriptional Repression ◽  
Embryonic Stem ◽  
Cardiac Differentiation ◽  
Heart Tube ◽  
Cardiac Progenitors ◽  
Gene Enhancer ◽  
Heart Field ◽  
Homeobox Protein ◽  
Islet 1

During heart development the second heart field (SHF) provides progenitor cells for most cardiomyocytes and expresses the LIM-homeodomain transcription factor Islet-1 (Isl1) and the homeobox protein Nkx2-5. Here, we show that a direct repression of Isl1 transcription by Nkx2-5 is necessary for proper specification and maturation of ventricular and atrial chamber-specific myocardial lineages. Overexpression of Nkx2-5 in mouse embryonic stem cells (ESCs) delayed specification of cardiac progenitors and inhibited expression of Isl1 and its downstream targets in the Isl1+ precursor population. These effects were partially rescued by Isl1 overexpression. Embryos deficient for Nkx2-5 in the Isl1+ lineage failed to downregulate Isl1 protein in cardiomyocytes of the heart tube (Figure 1A). We demonstrated that Nkx2-5 directly binds to an Isl1 gene enhancer and represses the transcriptional activity of Isl1. Furthermore, we showed that overexpression of Isl1 does not prevent cardiac differentiation of ESCs and in Xenopus laevis embryos. Instead, Isl1 overexpression in ESCs leads to enhanced specification of cardiac progenitors, earlier cardiac differentiation, and increased number of cardiomyocytes (Figure 1B). Functional and molecular analysis of Isl1-overexpressing cardiomyocytes revealed higher beating frequencies in both ESC-derived contracting areas and Xenopus Isl1-gain-of-function hearts (Figure 1C), which was associated with upregulation of nodal-specific genes and downregulation of transcripts of working myocardium. Our findings provide an Isl1/Nkx2-5-mediated mechanism that coordinately regulates the specification of cardiac progenitors towards the different myocardial lineages and ensures proper acquisition of myocyte subtype-identity (Figure 1D).

Deficiency in endothelial nitric oxide synthase impairs myocardial angiogenesis

2002 ◽  
Vol 283 (6) ◽  
pp. H2371-H2378 ◽  
Author(s):  
Xue Zhao ◽  
Xiangru Lu ◽  
Qingping Feng
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Heart Development ◽  
Tube Formation ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Wild Type ◽  
Endothelial Nitric Oxide

We recently demonstrated that mice deficient in endothelial nitric oxide (NO) synthase (eNOS) have congenital septal defects and postnatal heart failure. However, the mechanisms by which eNOS affects heart development are not clear. We hypothesized that deficiency in eNOS impairs myocardial angiogenesis. Myocardial capillary densities were measured morphometrically in neonatal mouse hearts. In vitro tube formation on Matrigel was investigated in cardiac endothelial cells. In vivo myocardial angiogenesis was performed by implanting Matrigel in the left ventricular myocardium. Myocardial capillary densities and VEGF mRNA expression were decreased in neonatal eNOS−/− compared with neonatal wild-type mice ( P < 0.01). Furthermore, in vitro tube formation from cardiac endothelial cells and in vivo myocardial angiogenesis were attenuated in eNOS−/− compared with wild-type mice ( P < 0.01). In vitro tube formation was inhibited by N G-nitro-l-arginine methyl ester in wild-type mice and restored by a NO donor, diethylenetriamine-NO, in eNOS−/− mice ( P < 0.05). In conclusion, deficiency in eNOS decreases VEGF expression and impairs myocardial angiogenesis and capillary development. Decreased myocardial angiogenesis may contribute to cardiac abnormalities during heart development in eNOS−/− mice.

scholarly journals Pseudo-dynamic analysis of heart tube formation in the mouse reveals strong regional variability and early left-right asymmetry

2021 ◽  
Author(s):  
Isaac Esteban ◽  
Patrick Schmidt ◽  
Susana Temino ◽  
Leif Kobbelt ◽  
Miguel Torres
Keyword(s):  
Heart Development ◽  
Computer Modelling ◽  
Morphological Variability ◽  
Tube Formation ◽  
Morphological Description ◽  
Heart Tube ◽  
Regional Variability ◽  
Mammalian Embryo ◽  
Morphological Variations ◽  
Left Right Asymmetry

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.

Cardiovascular development in the zebrafish. I. Myocardial fate map and heart tube formation

Development ◽  
1993 ◽  
Vol 119 (1) ◽  
pp. 31-40 ◽  
Author(s):  
D.Y. Stainier ◽  
R.K. Lee ◽  
M.C. Fishman
Keyword(s):  
Single Cell ◽  
Tube Formation ◽  
Cardiovascular Development ◽  
Heart Tube ◽  
Cell Stage ◽  
Animal Pole ◽  
Cardiac Progenitors ◽  
Somite Stage ◽  
The Future ◽  
Heart Tube Formation

We have analyzed the origin of cardiac progenitors in the zebrafish embryo by injection of single blastomeres with a lineage tracer dye, and examined the formation of the zebrafish heart tube by serial sectioning of immunostained embryos. At the 512-cell stage (early blastula), most cardiac progenitors lie in a marginal zone that extends from 90 degrees longitude (midway between the future dorsal and ventral axis) through 180 degrees longitude (the future ventral axis) to 270 degrees longitude. By focusing on myocardial progenitors located at 90 degrees (and 270 degrees) longitude, we found that a single cell injected in the early blastula can contribute progeny to both the atrium and ventricle. A cell injected in the midblastula contributes progeny to either the atrium or ventricle, but not both. This analysis suggests that, at least for these myocardial progenitors, the atrial and ventricular lineages separate in the midblastula. Precardiac cells involute early during gastrulation and turn towards the animal pole with other early involuting cells. These cardiogenic cells reach the embryonic axis around the 8-somite stage, and there they coalesce to form a pair of myocardial tubular primordia on either side of the midline. By the 21-somite stage, the tropomyosin-immunoreactive myocardial tubes have moved closer to each other, and a distinct group of cells, the endocardial progenitor cells, sits medially between them. The myocardial tubes then fuse to enclose the endocardial cells and form the definitive heart tube. By 22 hours postfertilization (26-somite stage), the heart tube is clearly beating. The regionalization of cardiac myosin heavy chain expression distinguishes the cardiac chambers at this stage, although they are not morphologically delineated until 36 hours. This work shows that cardiogenic regions can be identified in the early blastula, and that chamber restriction seems to arise in the midblastula. Additionally, it provides the basis for embryological perturbation at the single cell level, as well as for the genetic analysis of heart tube formation in the zebrafish.

scholarly journals Pro-Angiogenic Effects of Resveratrol in Brain Endothelial Cells: Nitric Oxide-Mediated Regulation of Vascular Endothelial Growth Factor and Metalloproteinases

2012 ◽  
Vol 32 (5) ◽  
pp. 884-895 ◽  
Author(s):  
Fabricio Simão ◽  
Aline S Pagnussat ◽  
Ji Hae Seo ◽  
Deepti Navaratna ◽  
Wendy Leung ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Tube Formation ◽  
Mitogen Activated Protein Kinase ◽  
Vascular Endothelial ◽  
Cerebral Endothelial Cells ◽  
Endothelial Growth Factor

Resveratrol may be a powerful way of protecting the brain against a wide variety of stress and injury. Recently, it has been proposed that resveratrol not only reduces brain injury but also promotes recovery after stroke. But the underlying mechanisms are unclear. Here, we tested the hypothesis that resveratrol promotes angiogenesis in cerebral endothelial cells and dissected the signaling pathways involved. Treatment of cerebral endothelial cells with resveratrol promoted proliferation, migration, and tube formation in Matrigel assays. Consistent with these pro-angiogenic responses, resveratrol altered endothelial morphology resulting in cytoskeletal rearrangements of β-catenin and VE-cadherin. These effects of resveratrol were accompanied by activation of phosphoinositide 3 kinase (PI3-K)/Akt and Mitogen-Activated Protein Kinase (MAPK)/ERK signaling pathways that led to endothelial nitric oxide synthase upregulation and increased nitric oxide (NO) levels. Subsequently, elevated NO signaling increased vascular endothelial growth factor and matrix metalloproteinase levels. Sequential blockade of these signaling steps prevented resveratrol-induced angiogenesis in cerebral endothelial cells. These findings provide a mechanistic basis for the potential use of resveratrol as a candidate therapy to promote angiogenesis and neurovascular recovery after stroke.

Hypothermia-induced cardioprotection using extended ischemia and early reperfusion cooling

2007 ◽  
Vol 292 (4) ◽  
pp. H1995-H2003 ◽  
Author(s):  
Zuo-Hui Shao ◽  
Wei-Tien Chang ◽  
Kim Chai Chan ◽  
Kim R. Wojcik ◽  
Chin-Wang Hsu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase ◽  
Therapeutic Hypothermia ◽  
Optimal Timing ◽  
No Production ◽  
Early Reperfusion ◽  
No Signaling ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Pkc Activation

Optimal timing of therapeutic hypothermia for cardiac ischemia is unknown. Our prior work suggests that ischemia with rapid reperfusion (I/R) in cardiomyocytes can be more damaging than prolonged ischemia alone. Also, these cardiomyocytes demonstrate protein kinase C (PKC) activation and nitric oxide (NO) signaling that confer protection against I/R injury. Thus we hypothesized that hypothermia will protect most using extended ischemia and early reperfusion cooling and is mediated via PKC and NO synthase (NOS). Chick cardiomyocytes were exposed to an established model of 1-h ischemia/3-h reperfusion, and the same field of initially contracting cells was monitored for viability and NO generation. Normothermic I/R resulted in 49.7 ± 3.4% cell death. Hypothermia induction to 25°C was most protective (14.3 ± 0.6% death, P < 0.001 vs. I/R control) when instituted during extended ischemia and early reperfusion, compared with induction after reperfusion (22.4 ± 2.9% death). Protection was completely lost if onset of cooling was delayed by 15 min of reperfusion (45.0 ± 8.2% death). Extended ischemia/early reperfusion cooling was associated with increased and sustained NO generation at reperfusion and decreased caspase-3 activation. The NOS inhibitor Nω-nitro-l-arginine methyl ester (200 μM) reversed these changes and abrogated hypothermia protection. In addition, the PKCε inhibitor myr-PKCε v1-2 (5 μM) also reversed NO production and hypothermia protection. In conclusion, therapeutic hypothermia initiated during extended ischemia/early reperfusion optimally protects cardiomyocytes from I/R injury. Such protection appears to be mediated by increased NO generation via activation of protein kinase Cε; nitric oxide synthase.

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