scholarly journals Genetic Steps to Organ Laterality in Zebrafish

2001 ◽  
Vol 2 (2) ◽  
pp. 60-68 ◽  
Author(s):  
Jau-Nian Chen ◽  
Frauke van Bebber ◽  
Allan M. Goldstein ◽  
Fabrizio C. Serluca ◽  
Donald Jackson ◽  
...  
Keyword(s):  
Genetic Screen ◽  
Visceral Organ ◽  
Heart Tube ◽  
Internal Organs ◽  
Body Form ◽  
Recessive Mutations ◽  
Class 1 ◽  
Liver And Pancreas ◽  
Left Right Asymmetry ◽  
Organ Laterality

All internal organs are asymmetric along the left–right axis. Here we report a genetic screen to discover mutations which perturb organ laterality. Our particular focus is upon whether, and how, organs are linked to each other as they achieve their laterally asymmetric positions. We generated mutations by ENU mutagenesis and examined F3 progeny using a cocktail of probes that reveal early primordia of heart, gut, liver and pancreas. From the 750 genomes examined, we isolated seven recessive mutations which affect the earliest left–right positioning of one or all of the organs. None of these mutations caused discernable defects elsewhere in the embryo at the stages examined. This is in contrast to those mutations we reported previously (Chenet al., 1997) which, along with left–right abnormalities, cause marked perturbation in gastrulation, body form or midline structures. We find that the mutations can be classified on the basis of whether they perturb relationships among organ laterality. In Class 1 mutations, none of the organs manifest any left–right asymmetry. The heart does not jog to the left and normally leftpredominantBMP4in the early heart tube remains symmetric. The gut tends to remain midline. There frequently is a remarkable bilateral duplication of liver and pancreas. Embryos with Class 2 mutations have organotypic asymmetry but, in any given embryo, organ positions can be normal, reversed or randomized. Class 3 reveals a hitherto unsuspected gene that selectively affects laterality of heart. We find that visceral organ positions are predicted by the direction of the preceding cardiac jog. We interpret this as suggesting that normally there is linkage between cardiac and visceral organ laterality. Class 1 mutations, we suggest, effectively remove the global laterality signals, with the consequence that organ positions are effectively symmetrical. Embryos with Class 2 mutations do manifest linkage among organs, but it may be reversed, suggesting that the global signals may be present but incorrectly orientated in some of the embryos. That laterality decisions of organs may be independently perturbed, as in the Class 3 mutation, indicates that there are distinctive pathways for reception and organotypic interpretation of the global signals.

scholarly journals Twisting of the zebrafish heart tube during cardiac looping is a tbx5-dependent and tissue-intrinsic process

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Federico Tessadori ◽  
Erika Tsingos ◽  
Enrico Sandro Colizzi ◽  
Fabian Kruse ◽  
Susanne C van den Brink ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Loss Of Function ◽  
Heart Tube ◽  
Atrioventricular Canal ◽  
Internal Organs ◽  
Cardiac Looping ◽  
Tissue Patterning ◽  
Ex Vivo Culture ◽  
Left Right Asymmetry ◽  
Organ Laterality

Organ laterality refers to the left-right asymmetry in disposition and conformation of internal organs and is established during embryogenesis. The heart is the first organ to display visible left-right asymmetries through its left-sided positioning and rightward looping. Here, we present a new zebrafish loss-of-function allele for tbx5a, which displays defective rightward cardiac looping morphogenesis. By mapping individual cardiomyocyte behavior during cardiac looping, we establish that ventricular and atrial cardiomyocytes rearrange in distinct directions. As a consequence, the cardiac chambers twist around the atrioventricular canal resulting in torsion of the heart tube, which is compromised in tbx5a mutants. Pharmacological treatment and ex vivo culture establishes that the cardiac twisting depends on intrinsic mechanisms and is independent from cardiac growth. Furthermore, genetic experiments indicate that looping requires proper tissue patterning. We conclude that cardiac looping involves twisting of the chambers around the atrioventricular canal, which requires correct tissue patterning by Tbx5a.

scholarly journals Antagonistic interactions in the zebrafish midline prior to the emergence of asymmetric gene expression are important for left–right patterning

2016 ◽  
Vol 371 (1710) ◽  
pp. 20150402 ◽  
Author(s):  
Rebecca D. Burdine ◽  
Daniel T. Grimes
Keyword(s):  
Gene Expression ◽  
Lateral Plate Mesoderm ◽  
Internal Organs ◽  
Lateral Plate ◽  
Left Right Asymmetry ◽  
Antagonistic Interactions

Left–right (L-R) asymmetry of the internal organs of vertebrates is presaged by domains of asymmetric gene expression in the lateral plate mesoderm (LPM) during somitogenesis. Ciliated L-R coordinators (LRCs) are critical for biasing the initiation of asymmetrically expressed genes, such as nodal and pitx2 , to the left LPM. Other midline structures, including the notochord and floorplate, are then required to maintain these asymmetries. Here we report an unexpected role for the zebrafish EGF-CFC gene one-eyed pinhead ( oep ) in the midline to promote pitx2 expression in the LPM. Late zygotic oep (LZ oep ) mutants have strongly reduced or absent pitx2 expression in the LPM, but this expression can be rescued to strong levels by restoring oep in midline structures only. Furthermore, removing midline structures from LZ oep embryos can rescue pitx2 expression in the LPM, suggesting the midline is a source of an LPM pitx2 repressor that is itself inhibited by oep . Reducing lefty1 activity in LZ oep embryos mimics removal of the midline, implicating lefty1 in the midline-derived repression. Together, this suggests a model where Oep in the midline functions to overcome a midline-derived repressor, involving lefty1 , to allow for the expression of left side-specific genes in the LPM. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’.

scholarly journals Cell chirality: emergence of asymmetry from cell culture

2016 ◽  
Vol 371 (1710) ◽  
pp. 20150413 ◽  
Author(s):  
Leo Q. Wan ◽  
Amanda S. Chin ◽  
Kathryn E. Worley ◽  
Poulomi Ray
Keyword(s):  
Cell Culture ◽  
Embryonic Development ◽  
Birth Defects ◽  
Controlled Experiments ◽  
Internal Organs ◽  
Recent Developments ◽  
Living Organisms ◽  
Left Right Asymmetry

Increasing evidence suggests that intrinsic cell chirality significantly contributes to the left–right (LR) asymmetry in embryonic development, which is a well-conserved characteristic of living organisms. With animal embryos, several theories have been established, but there are still controversies regarding mechanisms associated with embryonic LR symmetry breaking and the formation of asymmetric internal organs. Recently, in vitro systems have been developed to determine cell chirality and to recapitulate multicellular chiral morphogenesis on a chip. These studies demonstrate that chirality is indeed a universal property of the cell that can be observed with well-controlled experiments such as micropatterning. In this paper, we discuss the possible benefits of these in vitro systems to research in LR asymmetry, categorize available platforms for single-cell chirality and multicellular chiral morphogenesis, and review mathematical models used for in vitro cell chirality and its applications in in vivo embryonic development. These recent developments enable the interrogation of the intracellular machinery in LR axis establishment and accelerate research in birth defects in laterality. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’.

scholarly journals Heterotaxy in Caenorhabditis : widespread natural variation in left–right arrangement of the major organs

2016 ◽  
Vol 371 (1710) ◽  
pp. 20150404 ◽  
Author(s):  
Melissa R. Alcorn ◽  
Davon C. Callander ◽  
Agustín López-Santos ◽  
Yamila N. Torres Cleuren ◽  
Bilge Birsoy ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Recombinant Inbred Lines ◽  
Sensitive Period ◽  
Temperature Sensitive ◽  
Internal Organs ◽  
Genome Wide ◽  
A Genome ◽  
Natural Isolates ◽  
Left Right Asymmetry ◽  
Genomic Regions

Although the arrangement of internal organs in most metazoans is profoundly left–right (L/R) asymmetric with a predominant handedness, rare individuals show full (mirror-symmetric) or partial (heterotaxy) reversals. While the nematode Caenorhabditis elegans is known for its highly determinate development, including stereotyped L/R organ handedness, we found that L/R asymmetry of the major organs, the gut and gonad, varies among natural isolates of the species in both males and hermaphrodites. In hermaphrodites, heterotaxy can involve one or both bilaterally asymmetric gonad arms. Male heterotaxy is probably not attributable to relaxed selection in this hermaphroditic species, as it is also seen in gonochoristic Caenorhabditis species. Heterotaxy increases in many isolates at elevated temperature, with one showing a pregastrulation temperature-sensitive period, suggesting a very early embryonic or germline effect on this much later developmental outcome. A genome-wide association study of 100 isolates showed that male heterotaxy is associated with three genomic regions. Analysis of recombinant inbred lines suggests that a small number of loci are responsible for the observed variation. These findings reveal that heterotaxy is a widely varying quantitative trait in an animal with an otherwise highly stereotyped anatomy, demonstrating unexpected plasticity in an L/R arrangement of the major organs even in a simple animal. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’.

scholarly journals Standard Blood Tests Indicate Changes of Toxocariasis in Carnivores

2021 ◽  
Author(s):  
Olga Panova ◽  
Aleksandr Khrustalev ◽  
Natalia Sysoeva ◽  
Maria Baranova ◽  
Igor Glamazdin ◽  
...  
Keyword(s):  
Toxocara Canis ◽  
Blood Parameters ◽  
The Body ◽  
Internal Organs ◽  
Hematological Disorders ◽  
Blood Tests ◽  
Biochemical Studies ◽  
Liver And Pancreas

This study presents the main changes in the biochemical and hematological blood parameters of dogs and cats infected with toxocara. Presented data are based on the animal’s age and welfare. The authors conclude that the pattern of hematological disorders is most pronounced in young animals and proceeds with signs of general intoxication and sensibilizationof the body, hypoxia, anemia and damage to the internal organs (liver and pancreas). Keywords: hematological studies, biochemical studies, toxocariasis, Toxocara canis, T. cati

Genetic basis of human left–right asymmetry disorders

2014 ◽  
Vol 16 ◽  
Author(s):  
Hao Deng ◽  
Hong Xia ◽  
Sheng Deng
Keyword(s):  
Situs Inversus ◽  
Genetic Basis ◽  
Chromosomal Abnormalities ◽  
The Body ◽  
Disease Genes ◽  
Internal Organs ◽  
Abdominal Organs ◽  
Pathogenic Genes ◽  
Left Right Asymmetry ◽  
Reduced Penetrance

Humans and other vertebrates exhibit left–right (LR) asymmetric arrangement of the internal organs, and failure to establish normal LR asymmetry leads to internal laterality disorders, includingsitus inversusandheterotaxy.Situs inversusis complete mirror-imaged arrangement of the internal organs along LR axis, whereasheterotaxyis abnormal arrangement of the internal thoraco-abdominal organs across LR axis of the body, most of which are associated with complex cardiovascular malformations. Both disorders are genetically heterogeneous with reduced penetrance, presumably because of monogenic, polygenic or multifactorial causes. Research in genetics of LR asymmetry disorders has been extremely prolific over the past 17 years, and a series of loci and disease genes involved insitus inversusandheterotaxyhave been described. The review highlights the classification, chromosomal abnormalities, pathogenic genes and the possible mechanism of human LR asymmetry disorders.

Pitx2 determines left–right asymmetry of internal organs in vertebrates

Nature ◽  
10.1038/29004 ◽  
1998 ◽  
Vol 394 (6693) ◽  
pp. 545-551 ◽  
Author(s):  
Aimee K. Ryan ◽  
Bruce Blumberg ◽  
Concepción Rodriguez-Esteban ◽  
Sayuri Yonei-Tamura ◽  
Koji Tamura ◽  
...  
Keyword(s):  
Internal Organs ◽  
Left Right Asymmetry

scholarly journals MNS1 variant associated with situs inversus and male infertility

2019 ◽  
Vol 28 (1) ◽  
pp. 50-55 ◽  
Author(s):  
Joseph S. Leslie ◽  
Lettie E. Rawlins ◽  
Barry A. Chioza ◽  
Oluwaseun R. Olubodun ◽  
Claire G. Salter ◽  
...  
Keyword(s):  
Male Infertility ◽  
Situs Inversus ◽  
Autosomal Recessive ◽  
Internal Organs ◽  
Genome Wide ◽  
Whole Exome ◽  
Snp Mapping ◽  
Left Right Asymmetry ◽  
And Function ◽  
Laterality Defects

Abstract Ciliopathy disorders due to abnormalities of motile cilia encompass a range of autosomal recessive conditions typified by chronic otosinopulmonary disease, infertility, situs abnormalities and hydrocephalus. Using a combination of genome-wide SNP mapping and whole exome sequencing (WES), we investigated the genetic cause of a form of situs inversus (SI) and male infertility present in multiple individuals in an extended Amish family, assuming that an autosomal recessive founder variant was responsible. This identified a single shared (2.34 Mb) region of autozygosity on chromosome 15q21.3 as the likely disease locus, in which we identified a single candidate biallelic frameshift variant in MNS1 [NM_018365.2: c.407_410del; p.(Glu136Glyfs*16)]. Genotyping of multiple family members identified randomisation of the laterality defects in other homozygous individuals, with all wild type or MNS1 c.407_410del heterozygous carriers being unaffected, consistent with an autosomal recessive mode of inheritance. This study identifies an MNS1 variant as a cause of laterality defects and male infertility in humans, mirroring findings in Mns1-deficient mice which also display male infertility and randomisation of left–right asymmetry of internal organs, confirming a crucial role for MNS1 in nodal cilia and sperm flagella formation and function.

scholarly journals Nodal signalling and asymmetry of the nervous system

2016 ◽  
Vol 371 (1710) ◽  
pp. 20150401 ◽  
Author(s):  
Iskra A. Signore ◽  
Karina Palma ◽  
Miguel L. Concha
Keyword(s):  
Developmental Biology ◽  
Nervous System ◽  
Conceptual Framework ◽  
Detailed Analysis ◽  
Context Dependency ◽  
Directional Asymmetry ◽  
Visceral Organ ◽  
Left Right Asymmetry ◽  
The Brain

The role of Nodal signalling in nervous system asymmetry is still poorly understood. Here, we review and discuss how asymmetric Nodal signalling controls the ontogeny of nervous system asymmetry using a comparative developmental perspective. A detailed analysis of asymmetry in ascidians and fishes reveals a critical context-dependency of Nodal function and emphasizes that bilaterally paired and midline-unpaired structures/organs behave as different entities. We propose a conceptual framework to dissect the developmental function of Nodal as asymmetry inducer and laterality modulator in the nervous system, which can be used to study other types of body and visceral organ asymmetries. Using insights from developmental biology, we also present novel evolutionary hypotheses on how Nodal led the evolution of directional asymmetry in the brain, with a particular focus on the epithalamus. We intend this paper to provide a synthesis on how Nodal signalling controls left–right asymmetry of the nervous system. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’.

scholarly journals Applying Segmentation Pattern Analysis to Investigate Postprandial Plasma Glucose Characteristics and Behaviors of the Carbs/Sugar Intake Amounts In Different Nations (GH Method: Math-Physical Medicine)

2020 ◽  
Vol 5 (1) ◽  
Keyword(s):  
Plasma Glucose ◽  
Pattern Analysis ◽  
Communication Model ◽  
Physical Medicine ◽  
Internal Organs ◽  
Postprandial Plasma Glucose ◽  
Sugar Intake ◽  
Liver And Pancreas ◽  
Segmentation Pattern ◽  
The Brain

In this paper, the author presents the results of his national segmentation pattern analysis of the sensor PPG data based on both high-carb and low-carb intake amounts. It also verified his earlier findings on the communication model between the brain and internal organs such as the stomach, liver, and pancreas.

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