Linkage of cardiac left-right asymmetry and dorsal-anterior development in Xenopus

Development ◽  
1995 ◽  
Vol 121 (5) ◽  
pp. 1467-1474 ◽  
Author(s):  
M.C. Danos ◽  
H.J. Yost
Keyword(s):  
Cell Cycle ◽  
Spatial Patterns ◽  
Organizer Region ◽  
Common Mechanism ◽  
Contrast Injection ◽  
Dorsal Midline ◽  
Heart Looping ◽  
Left Right Asymmetry ◽  
Midline Cells ◽  
Anterior Posterior

The left-right body axis is defined relative to the dorsal-ventral and anterior-posterior body axes. Since left-right asymmetries are not randomly oriented with respect to dorsal-ventral and anterior-posterior spatial patterns, it is possible that a common mechanism determines all three axes in a coordinate manner. Two approaches were undertaken to determine whether alteration in dorsal-anterior development perturbs the left-right orientation of heart looping. Treatments known to decrease dorsal-anterior development in Xenopus laevis, UV irradiation during the first cell cycle or Xwnt-8 DNA injections into dorsal blastomeres, caused an increase in cardiac left-right reversals. The frequency of left-right reversal was correlated with the severity of dorsal-anterior perturbation and with the extent of anterior notochord regression. Injection of Xwnt-8 DNA into dorsal midline cells resulted in decreased dorsal-anterior development and a correlated increase in cardiac left-right reversals. In contrast, injection of Xwnt-8 DNA into cardiac progenitor blastomeres did not result in left-right reversals, and dorsal-anterior development and notochord formation were normal. Disrupting development of dorsal-anterior cells, including cells that give rise to the Organizer region and the notochord, results in the randomization of cardiac left-right asymmetry. These results suggest dorsal-anterior development and the regulation of left-right orientation are linked.

The anterior extent of dorsal development of the Xenopus embryonic axis depends on the quantity of organizer in the late blastula

Development ◽  
1990 ◽  
Vol 109 (2) ◽  
pp. 363-372 ◽  
Author(s):  
R.M. Stewart ◽  
J.C. Gerhart
Keyword(s):  
Xenopus Laevis ◽  
Cell Population ◽  
Marginal Zone ◽  
Organizer Region ◽  
Blastula Stage ◽  
Dorsal Midline ◽  
Anterior Dorsal ◽  
Lateral Width ◽  
Anterior Extent ◽  
Anterior Posterior

In amphibian gastrulae, the cell population of the organizer region of the marginal zone (MZ) establishes morphogenesis and patterning within itself and within surrounding regions of the MZ, presumptive neurectoderm, and archenteron roof. We have tested the effects on pattern of reducing the amount of organizer region by recombining halves of Xenopus laevis late blastulae cut at different angles from the bilateral plane. When regions within 30 degrees of the dorsal midline are excluded from recombinants, ventralized embryos develop lacking the entire anterior-posterior sequence of dorsal structures, suggesting that the organizer is only 60 degrees wide (centered on the dorsal midline) at the late blastula stage. As more and more dorsal MZ (organizer) is included in the recombinant, progressively more anterior dorsal structures are formed. In all cases, when any dorsal structures are missing they are deleted serially from the anterior end. Thus, we suggest that the amount (lateral width) of the organizer in the MZ determines the anterior extent of dorsal development.

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 Oriented cell divisions and cellular morphogenesis in the zebrafish gastrula and neurula: a time-lapse analysis

Development ◽  
1998 ◽  
Vol 125 (6) ◽  
pp. 983-994 ◽  
Author(s):  
M.L. Concha ◽  
R.J. Adams
Keyword(s):  
Cell Division ◽  
Time Lapse ◽  
Ventral Surface ◽  
Neural Plate ◽  
Common Mechanism ◽  
Gradual Transition ◽  
Animal Pole ◽  
Dorsal Midline ◽  
Vegetal Pole ◽  
The Central Nervous System

We have taken advantage of the optical transparency of zebrafish embryos to investigate the patterns of cell division, movement and shape during early stages of development of the central nervous system. The surface-most epiblast cells of gastrula and neurula stage embryos were imaged and analysed using a computer-based, time-lapse acquisition system attached to a differential interference contrast (DIC) microscope. We find that the onset of gastrulation is accompanied by major changes in cell behaviour. Cells collect into a cohesive sheet, apparently losing independent motility and integrating their behaviour to move coherently over the yolk in a direction that is the result of two influences: towards the vegetal pole in the movements of epiboly and towards the dorsal midline in convergent movements that strengthen throughout gastrulation. Coincidentally, the plane of cell division becomes aligned to the surface plane of the embryo and oriented in the anterior-posterior (AP) direction. These behaviours begin at the blastoderm margin and propagate in a gradient towards the animal pole. Later in gastrulation, cells undergo increasingly mediolateral-directed elongation and autonomous convergence movements towards the dorsal midline leading to an enormous extension of the neural axis. Around the equator and along the dorsal midline of the gastrula, persistent AP orientation of divisions suggests that a common mechanism may be involved but that neither oriented cell movements nor shape can account for this alignment. When the neural plate begins to differentiate, there is a gradual transition in the direction of cell division from AP to the mediolateral circumference (ML). ML divisions occur in both the ventral epidermis and dorsal neural plate. In the neural plate, ML becomes the predominant orientation of division during neural keel and nerve rod stages and, from late neural keel stage, divisions are concentrated at the dorsal midline and generate bilateral progeny (C. Papan and J. A. Campos-Ortega (1994) Roux's Arch. Dev. Biol. 203, 178–186). Coincidentally, cells on the ventral surface also orient their divisions in the ML direction, cleaving perpendicular to the direction in which they are elongated. The ML alignment of epidermal divisions is well correlated with cell shape but ML divisions within the neuroepithelium appear to be better correlated with changes in tissue morphology associated with neurulation.

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 Transcriptomic Analysis Reveals Both Coxsackievirus B3 Woodruff and GD Strain Using Similar Key Genes to Induce FoxO Signaling Pathway Activation in HeLa Cells

2021 ◽  
Author(s):  
Mi Liu ◽  
Qian Yang ◽  
Jun Han
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Signaling Pathway ◽  
Hela Cells ◽  
Stress Resistance ◽  
Coxsackievirus B3 ◽  
Common Mechanism ◽  
Oxidative Stress Resistance ◽  
Key Genes ◽  
Foxo Signaling Pathway

Abstract Coxsackievirus B3 (CVB3) is the major cause of viral myocarditis in human worldwide. Various studies have investigated the viral infection and pathogenic mechanisms. However, the precise disease mechanism is still not clear. In this study, RNA-seq technology was used to compare the transcriptomic profile of virus infected HeLa cells to the controls in order to analysis the key genes of host virus interaction. Two CVB3 strains, CVB3 Woodruff and GD16-69-CVB3 strain were selected to figure out the common disease mechanisms of both experimental and clinical strains respectively. Increased expression of cell cycle genes CCNG2, GADD45B, PIM1, RBM15, KLF10 and RIOK3, down regulation of CYBA were detected. Autophagy genes ATG12 and YOD1 were also upregulated during CVB3 infection. Slightly increase of SOD2 and ATG12 were shown in the expression of infected cells, meanwhile, little change was detected in GABARAP expression. Further, FoxO signaling pathway was enriched by KEGG analysis, shown a close interaction with the DEGs in the PPI network. Genes of related pathways such as cell cycle, autophagy and oxidative stress resistance were confirmed by RT-PCR as well. In conclusion, our results reveal that FoxO signaling pathway is a common mechanism activated during the infection of both CVB3 strains. And this pathway plays a regulatory role in downstream pathways such as cell cycle, autophagy, oxidative stress resistance and antiviral immune responds.

scholarly journals Cell cycle regulation of the cyclin A, cdc25C and cdc2 genes is based on a common mechanism of transcriptional repression.

1995 ◽  
Vol 14 (18) ◽  
pp. 4514-4522 ◽  
Author(s):  
J. Zwicker ◽  
F. C. Lucibello ◽  
L. A. Wolfraim ◽  
C. Gross ◽  
M. Truss ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcriptional Repression ◽  
Cell Cycle Regulation ◽  
Cyclin A ◽  
Common Mechanism ◽  
Cycle Regulation

Genes involved in forebrain development in the zebrafish, Danio rerio

Development ◽  
1996 ◽  
Vol 123 (1) ◽  
pp. 191-203 ◽  
Author(s):  
C.P. Heisenberg ◽  
M. Brand ◽  
Y.J. Jiang ◽  
R.M. Warga ◽  
D. Beuchle ◽  
...  
Keyword(s):  
Danio Rerio ◽  
Embryonic Axis ◽  
Dorsal Midline ◽  
Forebrain Development ◽  
Roof Plate ◽  
Partial Fusion ◽  
Anterior Forebrain ◽  
Plate Analysis ◽  
Midline Cells ◽  
Mutant Phenotypes

We identified four zebrafish mutants with defects in forebrain induction and patterning during embryogenesis. The four mutants define three genes: masterblind (mbl), silberblick (slb), and knollnase (kas). In mbl embryos, the anterior forebrain acquires posterior forebrain characteristics: anterior structures such as the eyes, olfactory placodes and the telencephalon are missing, whereas the epiphysis located in the posterior forebrain is expanded. In slb embryos, the extension of the embryonic axis is initially delayed and eventually followed by a partial fusion of the eyes. Finally, in kas embryos, separation of the telencephalic primordia is incomplete and dorsal midline cells fail to form a differentiated roof plate. Analysis of the mutant phenotypes indicates that we have identified genes essential for the specification of the anterior forebrain (mbl), positioning of the eyes (slb) and differentiation of the roof plate (kas). In an appendix to this study we list mutants showing alterations in the size of the eyes and abnormal differentiation of the lenses.

Retinoic acid is required in the mouse embryo for left-right asymmetry determination and heart morphogenesis

Development ◽  
1999 ◽  
Vol 126 (12) ◽  
pp. 2589-2596 ◽  
Author(s):  
C. Chazaud ◽  
P. Chambon ◽  
P. Dolle
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Mouse Embryo ◽  
Time Course ◽  
Retinoic Acid Receptor ◽  
Mouse Embryos ◽  
Anteroposterior Patterning ◽  
Heart Looping ◽  
Left Right Asymmetry

Determination of the left-right position (situs) of visceral organs involves lefty, nodal and Pitx2 genes that are specifically expressed on the left side of the embryo. We demonstrate that the expression of these genes is prevented by the addition of a retinoic acid receptor pan-antagonist to cultured headfold stage mouse embryos, whereas addition of excess retinoic acid leads to their symmetrical expression. Interestingly, both treatments lead to randomization of heart looping and to defects in heart anteroposterior patterning. A time course analysis indicates that only the newly formed mesoderm at the headfold-presomite stage is competent for these retinoid effects. We conclude that retinoic acid, the active derivative of vitamin A, is essential for heart situs determination and morphogenesis.

Left-right asymmetry in C. elegans intestine organogenesis involves a LIN-12/Notch signaling pathway

Development ◽  
2000 ◽  
Vol 127 (16) ◽  
pp. 3429-3440 ◽  
Author(s):  
G.J. Hermann ◽  
B. Leung ◽  
J.R. Priess
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway ◽  
Early Embryogenesis ◽  
C Elegans ◽  
Asymmetrical Pattern ◽  
Left Right Asymmetry ◽  
The Right ◽  
Sister Cells ◽  
Anterior Posterior

The C. elegans intestine is a simple tube consisting of a monolayer of epithelial cells. During embryogenesis, cells in the anterior of the intestinal primordium undergo reproducible movements that lead to an invariant, asymmetrical ‘twist’ in the intestine. We have analyzed the development of twist to determine how left-right and anterior-posterior asymmetries are generated within the intestinal primordium. The twist requires the LIN-12/Notch-like signaling pathway of C. elegans. All cells within the intestinal primordium initially express LIN-12, a receptor related to Notch; however, only cells in the left half of the primordium contact external, nonintestinal cells that express LAG-2, a ligand related to delta. LIN-12 and LAG-2 mediated interactions result in the left primordial cells expressing lower levels of LIN-12 than the right primordial cells. We propose that this asymmetrical pattern of LIN-12 expression is the basis for asymmetry in later cell-cell interactions within the primordium that lead directly to intestinal twist. Like the interactions that initially establish LIN-12 asymmetry, the later interactions are mediated by LIN-12. The later interactions, however, involve a different ligand related to delta, called APX-1. We show that the anterior-posterior asymmetry in intestinal twist involves the kinase LIT-1, which is part of a signaling pathway in early embryogenesis that generates anterior-posterior differences between sister cells.

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