Left-right asymmetry of a nodal-related gene is regulated by dorsoanterior midline structures during Xenopus development

Development ◽  
1997 ◽  
Vol 124 (8) ◽  
pp. 1465-1472 ◽  
Author(s):  
J.L. Lohr ◽  
M.C. Danos ◽  
H.J. Yost
Keyword(s):  
Signaling Pathway ◽  
Expression Patterns ◽  
Large Population ◽  
Related Gene ◽  
Lateral Plate ◽  
Dorsal Midline ◽  
Cardiac Looping ◽  
Organ Systems ◽  
Left Right Asymmetry ◽  
The Right

Development of asymmetry along the left-right axis is a critical step in the formation of the vertebrate body plan. Disruptions of normal left-right patterning are associated with abnormalities of multiple organ systems, including significant congenital heart disease. The mouse nodal gene, and its homologues in chick and Xenopus, are among the first genes known to be asymmetrically expressed along the left-right axis before the development of organ asymmetry. Alterations in the expression pattern of mouse nodal and the chick homologue (cNR-1) have been associated with defects in the development of left-right asymmetry and cardiac looping (Levin, M., Johnson, R. L., Stern, C. D., Kuehn, M. and Tabin, C. (1995) Cell 82, 803–814; Collignon, J., Varlet, I. and Robertson, E. J. (1996) Nature 381, 155–158; Lowe, L. A., Supp, D. M., Sampath, K., Yokoyama, T., Wright, C. V. E., Potter, S. S., Overbeek, P. and Kuehn, M. R. (1996) Nature 381, 158–161). Here, we show that the normal expression patterns of the Xenopus nodal-related gene (Xnr-1) are variable in a large population of embryos and that Xnr-1 expression is altered by treatments that perturb normal left-right development. The incidence of abnormal Xnr-1 expression patterns correlates well with cardiac reversal rates in both control and experimentally treated Xenopus embryos. Furthermore, dorsal midline structures, including notochord and/or hypochord and neural floorplate, regulate Xnr-1 expression prior to the specification of cardiac left-right orientation by repression of Xnr-1 expression in the right lateral plate mesoderm during closure of the neural tube. The correlation of Xnr-1 expression and orientation of cardiac looping suggests that Xnr-1 is a component of the left-right signaling pathway required for the specification of cardiac orientation in Xenopus, and that dorsal midline structures normally act to repress the signaling pathway on the right side of the embryo.

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.

scholarly journals Melatonin Receptor 2 Promotes Lipid Metabolism of Cumulus-oocyte Complexes via the cAMP/PKA Pathway

2021 ◽  
Author(s):  
Jun-Xue Jin ◽  
Hong-Di Cui ◽  
Chao-Qian Jiang ◽  
Zi-Cheng Qi ◽  
Ya Bian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Energy Source ◽  
Lipid Metabolism ◽  
Signaling Pathway ◽  
Oocyte Maturation ◽  
Expression Patterns ◽  
Cumulus Cells ◽  
Related Gene ◽  
Melatonin Receptor ◽  
Significant Difference

Abstract Background: The importance of the processes of lipogenesis and lipolysis in providing an essential energy source during oocyte maturation is increasingly being recognized. Recent our studies have demonstrated that melatonin up-regulated lipid metabolism during oocyte maturation. Nevertheless, there is still limited information regarding the underlying molecular mechanisms of action of melatonin on lipid metabolism in porcine cumulus-oocyte complexes (COCs). Here, our aim was to investigate the effect of melatonin on COCs, and the melatonin receptor-mediated lipid metabolism signaling pathway.Materials/methods: To determine the melatonin-mediated lipolysis pathway in cumulus cells, COCs were treated with melatonin and the correlated metabolic responses were assessed using melatonin receptor-mediated signaling.Results: The results showed that exposure of COCs to melatonin during in vitro maturation significantly increased cumulus expansion index, blastocyst formation rate and total cell numbers/blastocyst, although nuclear maturation was no significant difference. The levels of proteins MT1, MT2, Gsα, PKA, and lipolysis-related factors (AGTL, HSL, PLIN A+B) were significantly increased by melatonin supplementation, and this effect was inhibited by simultaneous treatment with melatonin antagonists (luzindole or 4P-PDOT), although 4P-PDOT treatment did not completely block the effect of melatonin on MT1. Further, the gene expression patterns reflected their relevant protein levels in cumulus cells. Melatonin-mediated lipolysis could significantly reduce lipid droplets (LDs) numbers and increase fatty acid (FA) production and ATP levels by increasing the β-oxidation-related gene expression in cumulus cells. Simultaneously, melatonin significantly increased the amount of LDs, FAs, ATP, and enhanced the lipid metabolism-related gene expression in oocytes. Finally, the oocyte quality was improved by increasing GDF9, BMP15 and GSH and decreasing ROS levels.Conclusion: These findings revealed that the MT2-mediated cAMP/PKA signaling pathway promotes intracellular lipolysis and FA production in cumulus cells, which provided an essential energy source for COCs development.

The homeobox gene Pitx2: mediator of asymmetric left-right signaling in vertebrate heart and gut looping

Development ◽  
1999 ◽  
Vol 126 (6) ◽  
pp. 1225-1234 ◽  
Author(s):  
M. Campione ◽  
H. Steinbeisser ◽  
A. Schweickert ◽  
K. Deissler ◽  
F. van Bebber ◽  
...  
Keyword(s):  
Ectopic Expression ◽  
Homeobox Gene ◽  
Zebrafish Embryos ◽  
Lateral Plate Mesoderm ◽  
Lateral Plate ◽  
Left Right Asymmetry ◽  
The Right ◽  
Pitx2 Expression

Left-right asymmetry in vertebrates is controlled by activities emanating from the left lateral plate. How these signals get transmitted to the forming organs is not known. A candidate mediator in mouse, frog and zebrafish embryos is the homeobox gene Pitx2. It is asymmetrically expressed in the left lateral plate mesoderm, tubular heart and early gut tube. Localized Pitx2 expression continues when these organs undergo asymmetric looping morphogenesis. Ectopic expression of Xnr1 in the right lateral plate induces Pitx2 transcription in Xenopus. Misexpression of Pitx2 affects situs and morphology of organs. These experiments suggest a role for Pitx2 in promoting looping of the linear heart and gut.

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.

Regulation of midline development by antagonism of lefty and nodal signaling

Development ◽  
1999 ◽  
Vol 126 (14) ◽  
pp. 3253-3262 ◽  
Author(s):  
B.W. Bisgrove ◽  
J.J. Essner ◽  
H.J. Yost
Keyword(s):  
Expression Patterns ◽  
Ectopic Expression ◽  
Bilateral Symmetry ◽  
Expression Domain ◽  
Lateral Plate ◽  
Altered Expression ◽  
Left Right Asymmetry ◽  
Midline Development ◽  
Additional Role ◽  
Pitx2 Expression

The embryonic midline is crucial for the development of embryonic pattern including bilateral symmetry and left-right asymmetry. In zebrafish, lefty1 (lft1) and lefty2 (lft2) have distinct midline expression domains along the anteroposterior axis that overlap with the expression patterns of the nodal-related genes cyclops and squint. Altered expression patterns of lft1 and lft2 in zebrafish mutants that affect midline development suggests different upstream pathways regulate each expression domain. Ectopic expression analysis demonstrates that a balance of lefty and cyclops signaling is required for normal mesendoderm patterning and goosecoid, no tail and pitx2 expression. In late somite-stage embryos, lft1 and lft2 are expressed asymmetrically in the left diencephalon and left lateral plate respectively, suggesting an additional role in laterality development. A model is proposed by which the vertebrate midline, and thus bilateral symmetry, is established and maintained by antagonistic interactions among co-expressed members of the lefty and nodal subfamilies of TGF-beta signaling molecules.

BMP signaling positively regulates Nodal expression during left right specification in the chick embryo

Development ◽  
2002 ◽  
Vol 129 (14) ◽  
pp. 3431-3440 ◽  
Author(s):  
M. Elisa Piedra ◽  
Mana A. Ros
Keyword(s):  
Bmp Signaling ◽  
Lateral Plate Mesoderm ◽  
Lateral Plate ◽  
Positive Role ◽  
Molecular Control ◽  
Left And Right ◽  
Left Right Asymmetry ◽  
The Right ◽  
Rapid Activation ◽  
Positive Effect

Exogenous application of BMP to the lateral plate mesoderm (LPM) of chick embryos at the early somite stage had a positive effect on Nodal expression. BMP applications into the right LPM were followed by a rapid activation of Nodal, while applications into the left LPM resulted in expansion of the normal domain of Nodal expression. Conversely, blocking of BMP signaling by Noggin in the left LPM interfered with the activation of Nodal expression. These results support a positive role for endogenous BMP on Nodal expression in the LPM. We also report that BMP positively regulates the expression of Caronte, Snail and Cfc in both the left and right LPM. BMP-treated embryos had molecular impairment of the midline with downregulation of Lefty1, Brachyury and Shh but we also show that the midline defect was not sufficient to induce ectopic Nodal expression. We discuss our findings in the context of the known molecular control of the specification of left-right asymmetry.

scholarly journals A Xenopus nodal-related gene that acts in synergy with noggin to induce complete secondary axis and notochord formation

Development ◽  
1996 ◽  
Vol 122 (10) ◽  
pp. 3275-3282 ◽  
Author(s):  
K.D. Lustig ◽  
K. Kroll ◽  
E. Sun ◽  
R. Ramos ◽  
H. Elmendorf ◽  
...  
Keyword(s):  
Ectopic Expression ◽  
Signaling Proteins ◽  
Secreted Protein ◽  
Lateral Plate Mesoderm ◽  
Related Gene ◽  
Lateral Plate ◽  
Secondary Axis ◽  
Muscle Formation ◽  
Tailbud Stage ◽  
Left Right Asymmetry

Using a paracrine assay to screen for signaling proteins that could respecify ectodermal tissue, we isolated a Xenopus gene related to the mouse gene nodal, a member of the TGFbeta superfamily. The gene is expressed in three regions in the early Xenopus embryo: first in the gastrula organizer, then in two stripes of cells flanking the posterior notochord in late neurulae, and finally in lateral plate mesoderm restricted to the left side of tailbud-stage embryos. Ectopic expression of the gene induces muscle formation in ectodermal explants and partial secondary axes in whole embryos. Together with noggin, another secreted protein also present in the organizer, it induces notochord formation in ectodermal explants and complete secondary axes in whole embryos. These results suggest that the nodal-related gene may act together with noggin to induce axial pattern during gastrulation and also may play a role in left-right asymmetry generation in the post-gastrula embryo.

The Effect of a Hydrocolloid Dressing on Second Intention Wound Healing in Cats

2018 ◽  
Vol 54 (3) ◽  
pp. 125-131 ◽  
Author(s):  
Vassiliki Tsioli ◽  
Pagona G. Gouletsou ◽  
Apostolos D. Galatos ◽  
Dimitra Psalla ◽  
Antonios Lymperis ◽  
...  
Keyword(s):  
Wound Healing ◽  
Clinical Evaluation ◽  
The Other ◽  
Skin Wounds ◽  
Tissue Formation ◽  
Dorsal Midline ◽  
Granulation Tissue Formation ◽  
Hydrocolloid Dressing ◽  
Thickness Skin ◽  
The Right

ABSTRACT The objective of the present study was to evaluate the effect of a hydrocolloid dressing on second intention wound healing in cats. Two full-thickness skin wounds, measuring 2 × 2 cm, were created on both sides of the dorsal midline of 10 cats; bilaterally, one randomly selected wound was bandaged with a hydrocolloid dressing and the second one (control) with a semiocclusive pad. Subjective clinical evaluation of granulation tissue formation, of the quantity and nature of wound exudate, and planimetry were performed on the right-side wounds, and histological examination on the left. No significant differences in subjective clinical evaluation or in planimetry were observed between the hydrocolloid-treated wounds and controls. Most wounds had serous or absence of exudate (41.25% and 25%, respectively), whereas purulent exudate was observed in 7.5% of wounds. Edema was significantly increased in the hydrocolloid-treated wounds compared with controls on day 7 but no significant differences in the other histological variables were observed.

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