scholarly journals Directionality of Heart Looping: Effects of Pitx2c Misexpression on Flectin Asymmetry and Midline Structures

2002 ◽  
Vol 246 (2) ◽  
pp. 407-417 ◽  
Author(s):  
Kersti K. Linask ◽  
Xueyan Yu ◽  
YiPing Chen ◽  
Ming-Da Han
Keyword(s):  
Heart Looping

scholarly journals Functional Morphology of the Cardiac Jelly in the Tubular Heart of Vertebrate Embryos

2019 ◽  
Author(s):  
Jörg Männer ◽  
Talat Mesud Yelbuz
Keyword(s):  
Spatial Distribution ◽  
Cross Sections ◽  
Embryonic Heart ◽  
Endocardial Cushions ◽  
Valveless Pumping ◽  
Matrix Layer ◽  
Heart Looping ◽  
Biological Aspects ◽  
Vertebrate Embryos ◽  
Heart Wall

The early embryonic heart is a multi-layered tube consisting of (1) an outer myocardial tube; (2) an inner endocardial tube; and (3) an extracellular matrix layer interposed between myocardium and endocardium, called “cardiac jelly” (CJ). During the past decades, research on CJ has mainly focused on its molecular and cell biological aspects. This review focuses on the morphological and biomechanical aspects of CJ. Special attention is given to (1) the spatial distribution and fiber architecture of CJ; (2) the morphological dynamics of CJ during the cardiac cycle; and (3) the removal/remodeling of CJ during advanced heart looping stages, which leads to the formation of ventricular trabeculations and endocardial cushions. CJ acts as a hydraulic skeleton displaying striking structural and functional similarities with the mesoglea of jellyfish. CJ not only represents a filler substance, facilitating end-systolic occlusion of the embryonic heart lumen. Its elastic components antagonize the systolic deformations of the heart wall and thereby power the refilling phase of the ventricular tube. Non-uniform spatial distribution of CJ generates non-circular cross sections of the opened endocardial tube (initially elliptic, later deltoid), which seem to be advantageous for valveless pumping. Endocardial cushions arise from non-removed remnants of the original CJ.

Cardiac looping and the vertebrate left-right axis: antagonism of left-sided Vg1 activity by a right-sided ALK2-dependent BMP pathway

Development ◽  
1999 ◽  
Vol 126 (23) ◽  
pp. 5195-5205 ◽  
Author(s):  
A.F. Ramsdell ◽  
H.J. Yost
Keyword(s):  
Signaling Pathway ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Xenopus Embryo ◽  
Receptor Expression ◽  
Heart Tube ◽  
Cardiac Morphogenesis ◽  
Heart Looping ◽  
Bmp Pathway ◽  
The Right

The rightward looping of the primary heart tube is dependent upon upstream patterning events that establish the vertebrate left-right axis. In Xenopus, a left-sided Vg1 signaling pathway has been implicated in instructing cells to adopt a ‘left-sided identity’; however, it is not known whether ‘right-sided identity’ is acquired by a default pathway or by antagonism of Vg1 signaling. Here, we propose that an antagonistic, BMP/ALK2/Smad-mediated signaling pathway is active on the right side of the Xenopus embryo. Truncated ALK2 receptor expression on the right side of the blastula elicits heart reversals and altered nodal expression. Consistent with these findings, constitutively active ALK2 (CA-ALK2) receptor expression on the left side of the blastula also elicits heart reversals and altered nodal expression. Coexpression of CA-ALK2 with mature Vg1 ligand results in predominantly left-sided nodal expression patterns and normal heart looping, demonstrating that the ALK2 pathway can ‘rescue’ left-right reversals that otherwise occur following right-sided misexpression of mature Vg1 ligand alone. Results with chimeric precursor proteins indicate that the mature domain of BMP ligands can mimic the ability of the ALK2 signaling pathway to antagonize the Vg1 pathway. Consistent with the observed antagonism between BMP and Vg1 ligands, left-sided ectopic expression of Xolloid results in heart reversals. Moreover, ectopic expression of Smad1 or Smad7 identified two downstream modulators of the BMP/ALK2 signaling pathway that also can regulate cardiac orientation. Collectively, these results define a BMP/ALK2-mediated pathway on the right side of the Xenopus embryo and, moreover, suggest that left-right patterning preceding cardiac morphogenesis involves the activation of two distinct and antagonistic, left- and right-sided TGF(beta)-related signaling pathways.

The cardiac homeobox gene Csx/Nkx2.5 lies genetically upstream of multiple genes essential for heart development

Development ◽  
1999 ◽  
Vol 126 (6) ◽  
pp. 1269-1280 ◽  
Author(s):  
M. Tanaka ◽  
Z. Chen ◽  
S. Bartunkova ◽  
N. Yamasaki ◽  
S. Izumo
Keyword(s):  
Cardiac Myocytes ◽  
Heart Development ◽  
Cardiac Development ◽  
Es Cells ◽  
Homeobox Gene ◽  
Yolk Sac ◽  
Tunel Staining ◽  
Mesoderm Specification ◽  
Developing Heart ◽  
Heart Looping

Csx/Nkx2.5 is a vertebrate homeobox gene with a sequence homology to the Drosophila tinman, which is required for the dorsal mesoderm specification. Recently, heterozygous mutations of this gene were found to cause human congenital heart disease (Schott, J.-J., Benson, D. W., Basson, C. T., Pease, W., Silberbach, G. M., Moak, J. P., Maron, B. J., Seidman, C. E. and Seidman, J. G. (1998) Science 281, 108–111). To investigate the functions of Csx/Nkx2.5 in cardiac and extracardiac development in the vertebrate, we have generated and analyzed mutant mice completely null for Csx/Nkx2.5. Homozygous null embryos showed arrest of cardiac development after looping and poor development of blood vessels. Moreover, there were severe defects in vascular formation and hematopoiesis in the mutant yolk sac. Interestingly, TUNEL staining and PCNA staining showed neither enhanced apoptosis nor reduced cell proliferation in the mutant myocardium. In situ hybridization studies demonstrated that, among 20 candidate genes examined, expression of ANF, BNP, MLC2V, N-myc, MEF2C, HAND1 and Msx2 was disturbed in the mutant heart. Moreover, in the heart of adult chimeric mice generated from Csx/Nkx2.5 null ES cells, there were almost no ES cell-derived cardiac myocytes, while there were substantial contributions of Csx /Nkx2.5-deficient cells in other organs. Whole-mount β-gal staining of chimeric embryos showed that more than 20% contribution of Csx/Nkx2. 5-deficient cells in the heart arrested cardiac development. These results indicate that (1) the complete null mutation of Csx/Nkx2.5 did not abolish initial heart looping, (2) there was no enhanced apoptosis or defective cell cycle entry in Csx/Nkx2.5 null cardiac myocytes, (3) Csx/Nkx2.5 regulates expression of several essential transcription factors in the developing heart, (4) Csx/Nkx2.5 is required for later differentiation of cardiac myocytes, (5) Csx/Nkx2. 5 null cells exert dominant interfering effects on cardiac development, and (6) there were severe defects in yolk sac angiogenesis and hematopoiesis in the Csx/Nkx2.5 null embryos.

scholarly journals Designer Nodal/BMP2 Chimeras Mimic Nodal Signaling, Promote Chondrogenesis, and Reveal a BMP2-like Structure

2013 ◽  
Vol 289 (3) ◽  
pp. 1788-1797 ◽  
Author(s):  
Luis Esquivies ◽  
Alissa Blackler ◽  
Macarena Peran ◽  
Concepcion Rodriguez-Esteban ◽  
Juan Carlos Izpisua Belmonte ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Chondrogenic Differentiation ◽  
Biochemical Study ◽  
Adipose Derived Stem Cells ◽  
Nodal Signaling ◽  
Induced Differentiation ◽  
Therapeutic Implications ◽  
Heart Looping ◽  
Cartilage Injuries ◽  
Left Right Asymmetry

Nodal, a member of the TGF-β superfamily, plays an important role in vertebrate and invertebrate early development. The biochemical study of Nodal and its signaling pathway has been a challenge, mainly because of difficulties in producing the protein in sufficient quantities. We have developed a library of stable, chemically refoldable Nodal/BMP2 chimeric ligands (NB2 library). Three chimeras, named NB250, NB260, and NB264, show Nodal-like signaling properties including dependence on the co-receptor Cripto and activation of the Smad2 pathway. NB250, like Nodal, alters heart looping during the establishment of embryonic left-right asymmetry, and both NB250 and NB260, as well as Nodal, induce chondrogenic differentiation of human adipose-derived stem cells. This Nodal-induced differentiation is shown to be more efficient than BPM2-induced differentiation. Interestingly, the crystal structure of NB250 shows a backbone scaffold similar to that of BMP2. Our results show that these chimeric ligands may have therapeutic implications in cartilage injuries.

scholarly journals A Role for the Cytoskeleton in Heart Looping

2007 ◽  
Vol 2 ◽  
pp. 29-46
Author(s):  
Kersti K. Linask ◽  
Michael VanAuker
Keyword(s):  
Heart Looping

scholarly journals Proprotein Convertase Furina Is Required for Heart Development in Zebrafish

2021 ◽  
Author(s):  
Qinchao Zhou ◽  
Lei Lei ◽  
Hefei Zhang ◽  
Shih-Ching Chiu ◽  
Lu Gao ◽  
...  
Keyword(s):  
Heart Development ◽  
Positional Cloning ◽  
Notch Receptor ◽  
Post Translational Modification ◽  
Proprotein Convertase ◽  
Cardiac Looping ◽  
Heart Looping ◽  
Pharyngeal Arch Arteries ◽  
Underlying Mechanisms ◽  
Mutant Phenotypes

Cardiac looping and trabeculation are key processes during cardiac chamber maturation. However, the underlying mechanisms remain incompletely understood. Here, we report the isolation, cloning, and characterization of the proprotein convertase furina from the cardiovascular mutant loft in zebrafish. loft is an ethylnitrosourea-induced mutant and has evident defects in the cardiac outflow tract, heart looping and trabeculation, the craniofacial region, and pharyngeal arch arteries. Positional cloning revealed that furina mRNA was barely detectable in loft mutants, and loft failed to complement the TALEN-induced furina mutant pku338, confirming that furina is responsible for the loft mutant phenotypes. Mechanistic studies demonstrated that Notch reporter Tg(tp1:mCherry) signals were largely eliminated in mutant hearts, while over-expression of NICD partially rescued the mutant phenotypes, probably due to the lack of Furina-mediated cleavage processing of Notch1b proteins, the only Notch receptor expressed in the heart. Together, our data suggest a potential post-translational modification of Notch1b proteins via the proprotein convertase Furina in the heart and unveil the function of the Furina-Notch1b axis in cardiac looping and trabeculation in zebrafish and possibly in other organisms.

scholarly journals The Oak Ridge Polycystic Kidney (orpk) disease gene is required for left-right axis determination

Development ◽  
2000 ◽  
Vol 127 (11) ◽  
pp. 2347-2355 ◽  
Author(s):  
N.S. Murcia ◽  
W.G. Richards ◽  
B.K. Yoder ◽  
M.L. Mucenski ◽  
J.R. Dunlap ◽  
...  
Keyword(s):  
Critical Role ◽  
Polycystic Kidney ◽  
Functional Feature ◽  
Knock Out ◽  
Oak Ridge ◽  
Hypomorphic Allele ◽  
Heart Looping ◽  
Left Right Asymmetry ◽  
Midline Development ◽  
Knockout Allele

Analysis of several mutations in the mouse is providing useful insights into the nature of the genes required for the establishment of the left-right axis during early development. Here we describe a new targeted allele of the mouse Tg737 gene, Tg737(Delta)2-3(beta)Gal), which causes defects in left-right asymmetry and other abnormalities during embryogenesis. The Tg737 gene was originally identified based on its association with the mouse Oak Ridge Polycystic Kidney (orpk) insertional mutation, which causes polycystic kidney disease and other defects. Complementation tests between the original orpk mutation and the new targeted knock-out mutation demonstrate that Tg737(Delta)2-3(beta)Gal) behaves as an allele of Tg737. The differences in the phenotype between the two mutations suggest that the orpk mutation is a hypomorphic allele of the Tg737 gene. Unlike the orpk allele, where all homozygotes survive to birth, embryos homozygous for the Tg737(Delta)2-3(beta)Gal) mutation arrest in development at mid-gestation and exhibit neural tube defects, enlargement of the pericardial sac and, most notably, left-right asymmetry defects. At mid-gestation the direction of heart looping is randomized, and at earlier stages in development lefty-2 and nodal, which are normally expressed asymmetrically, exhibit symmetrical expression in the mutant embryos. Additionally, we determined that the ventral node cells in mutant embryos fail to express the central cilium, which is a characteristic and potentially functional feature of these cells. The expression of both Shh and Hnf3(beta) is downregulated in the midline at E8.0, indicating that there are significant alterations in midline development in the Tg737(Delta)2-3(beta)Gal) homozygous embryos. We propose that the failure of ventral node cells to fully mature alters their ability to undergo differentiation as they migrate out of the node to contribute to the developing midline structures. Analysis of this new knockout allele allows us to define a critical role for the Tg737 gene during early embryogenesis. We have named the product of the Tg737 gene Polaris, which is based on the various polarity related defects associated with the different alleles of the Tg737 gene.

scholarly journals Isoniazid causes heart looping disorder of zebrafish embryo by inducing oxidative stress

2019 ◽  
Author(s):  
Hongye WANG ◽  
Liu Yihai ◽  
Wei Xiyi ◽  
cheng cao ◽  
Hu Tingting
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Underlying Mechanism ◽  
Control Group ◽  
Transgenic Zebrafish ◽  
Zebrafish Embryos ◽  
High Concentration ◽  
Negative Effects ◽  
Developing Heart ◽  
Heart Looping

Abstract The cardiotoxicity of isoniazid on zebrafish embryos and its underlying mechanism remained unclear. Here, we exposed zebrafish embryos at 4 hours post fertilization to different levels of isoniazid and recorded the morphology and number of malformed and dead embryos under the microscope. The high concentration of isoniazid group showed more malformed and dead embryos compared with low dose of isoniazid group and control group. Besides, the morphology of heart and its alteration were visualized using the transgenic zebrafish (cmlc2: GFP) and confirmed by in situ hybridization. The negative effects of isoniazid on the developing heart were characterized by lower heart rate and more heart looping disorders. Mechanistically, PCR showed decreased expression of heart-specific transcription factors exposed to isoniazid. Oxidative stress was induced by Isoniazid in cardiomyocytes, mediated by decreased activity of CAT and SOD, which could be rescued by ROS scavenger. In conclusion, we demonstrated that isoniazid lead to heart looping disturbance by downregulating cardiac specific transcription factors and inducing cardiomyocytes apoptosis.

Myofibrillogenesis and myofiber pattern in normal and angiotensin induced cardiac inversion in developing rat heart

1995 ◽  
Vol 53 ◽  
pp. 908-909
Author(s):  
RL Price ◽  
L Fu ◽  
DG Simpson ◽  
TK Borg ◽  
L Terracio
Keyword(s):  
Pattern Formation ◽  
In Utero ◽  
Confocal Scanning Laser Microscopy ◽  
Whole Embryo Culture ◽  
Image Reconstruction Techniques ◽  
Heart Looping ◽  
Coordinated Expression ◽  
Confocal Scanning ◽  
Confocal Scanning Laser

Myofibrillogenesis, myofiber pattern formation, and heart looping respond to physical, hormonal and teratogenic agents. In cell culture, myofibrillogenesis and myofiber pattern formation depend on coordinated expression of cytoskeletal and myofibrillar components and signals from extracellular matrix (ECM). However, these experiments have been conducted with isolated cardiac myocytes in which phenotype of myocytes is stellate rather than tubular as found in situ.Whole embryo culture (WEC) allows in situ interactions to occur during controlled application of perturbatory agents. Application of 10 μg/ml angiotensin to WEC results in 10% cardiac inversion (controls - 0% inversions). In this condition, hearts loop right, rather than left as in normal development. We are using confocal scanning laser microscopy (CSLM), transmission electron microscopy (TEM), and image reconstruction techniques to examine myofibrillogenesis and myofiber pattern formation in embryos allowed to develop in utero and WEC.Rat hearts 9.5 to 11.5 days in utero development, and hearts 9.5 days in utero and 48 H WEC were examined by CSLM and TEM.

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