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.

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.

Identifying targets of the rough homeobox gene of Drosophila: evidence that rhomboid functions in eye development

Development ◽  
1992 ◽  
Vol 116 (2) ◽  
pp. 335-346 ◽  
Author(s):  
M. Freeman ◽  
B.E. Kimmel ◽  
G.M. Rubin
Keyword(s):  
Cell Fate ◽  
Target Genes ◽  
Eye Development ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Homeobox Gene ◽  
Homeodomain Protein ◽  
Dorsoventral Patterning ◽  
Altered Expression ◽  
Enhancer Trap Lines

In order to identify potential target genes of the rough homeodomain protein, which is known to specify some aspects of the R2/R5 photoreceptor subtype in the Drosophila eye, we have carried out a search for enhancer trap lines whose expression is rough-dependent. We crossed 101 enhancer traps that are expressed in the developing eye into a rough mutant background, and have identified seven lines that have altered expression patterns. One of these putative rough target genes is rhomboid, a gene known to be required for dorsoventral patterning and development of some of the nervous system in the embryo. We have examined the role of rhomboid in eye development and find that, while mutant clones have only a subtle phenotype, ectopic expression of the gene causes the non-neuronal mystery cells to be transformed into photoreceptors. We propose that rhomboid is a part of a partially redundant network of genes that specify photoreceptor cell fate.

An early marker of axial pattern in the chick embryo and its respecification by retinoic acid

Development ◽  
1992 ◽  
Vol 114 (4) ◽  
pp. 841-852 ◽  
Author(s):  
O. Sundin ◽  
G. Eichele
Keyword(s):  
Retinoic Acid ◽  
Chick Embryo ◽  
Protein A ◽  
Ectopic Expression ◽  
Primitive Streak ◽  
Expression Domain ◽  
Lateral Plate ◽  
Antibody Staining ◽  
Discrete Band ◽  
Stage Embryo

Chick Ghox 2.9 protein, a homeodomain-containing polypeptide, is first detected in the mid-gastrula stage embryo and its levels increase rapidly in the late gastrula. At this time, the initially narrow band of expression along the primitive streak expands laterally to form a shield-like domain that encompasses almost the entire posterior region of the embryo and extends anteriorly as far as Hensen's node. We have found that this expression domain co-localizes with a morphological feature that consists of a stratum of refractile, thickened mesoderm. Antibody-staining indicates that Ghox 2.9 protein is present in all cells of this mesodermal region. In contrast, expression within the ectoderm overlying the region of refractile mesoderm varies considerably. The highest levels of expression are found in ectoderm near the streak and surrounding Hensen's node, regions that recent fate mapping studies suggest that primarily destined to give rise to neurectoderm. At the definitive streak stage (Hamburger and Hamilton stage 4) the chick embryo is especially sensitive to the induction of axial malformations by retinoic acid. Four hours after the treatment of definitive streak embryos with a pulse of retinoic acid the expression of Ghox 2.9 protein is greatly elevated. This ectopic expression occurs in tissues anterior to Hensen's node, including floor plate, notochord, presumptive neural plate and lateral plate mesoderm, but does not occur in the anteriormost region of the embryo. The ectopic induction of Ghox 2.9 is strongest in ectoderm, and weaker in the underlying mesoderm. Endoderm throughout the embryo is unresponsive. At stage 11, Ghox 2.9 is normally expressed at high levels within rhombomere 4 of the developing hindbrain. In retinoic-acid-treated embryos which have developed to this stage, typical rhombomere boundaries are largely absent. Nevertheless, Ghox 2.9 is still expressed as a discrete band, but one that is widened and displaced to a more anterior position.

Abstract 131: Differential Regulation of Pitx2 Expression in Pulmonary Vein Muscle Sleeves and Left Atrium with Aging: Implication for Pulmonary Vein Triggers

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Johnson Wong ◽  
Div Verma ◽  
Craig Selzman ◽  
Huei-sheng Vincent Chen
Keyword(s):  
Transcription Factor ◽  
Left Atrium ◽  
Pulmonary Vein ◽  
Expression Patterns ◽  
Ryanodine Receptors ◽  
Age Groups ◽  
Calcium Handling ◽  
Age Related ◽  
Left Right Asymmetry ◽  
Pitx2 Expression

Introduction: Pitx2, Paired-like homeodomain transcription factor 2, is a homeobox transcription factor that regulates left-right asymmetry during cardiogenesis. Pitx2 insufficiency in the left atrium (LA) has been linked to LA remodeling and arrhythmogenesis in age-related atrial fibrillation (AF). However, the main triggers for AF reside in pulmonary vein muscle sleeves (PVs). Whether Pitx2 insufficiency in PVs also plays a pathogenic role in generating trigger foci remains to be determined. Also, changes in Pitx2 expression in PVs with age remain unclear. We use qRT-PCR and Illumina microarrays to determine age-related changes in Pitx2 expression of PVs in wild type (WT) & heterozygous Pitx2cnull+/- mice, and in humans with or without AF. Methods: PV and LA regions were obtained from 1-23 month-old WT and Pitx2cnull+/- mice. Human PVs were obtained from ~110D human fetal hearts (E110D aborted fetus), two groups of adult donor hearts [20-30s year-old (yo) and 40-50 yo] and two patients with persistent AF. These tissues were used for genetic expression analysis. Results: Pitx2c expression decreases slightly with age in mouse LA and PV tissues. The expression levels of Pitx2c of Pitx2cnull+/- mice in LA are consistently at 55.2±10.5% of WT but at near-equal levels in PVs over four different age groups. In contrast, during human development, Pitx2 expression in PV muscle sleeves first decreases from ~E110D to ~30 yo but increases from 30 to 50 yo. In patients with AF, Pitx2 expression in PVs is only lower by 15% while HCN4 expression is higher by 13.5% when compared to control PVs at >50 yo. Expressions of type 2 Ryanodine receptors and calsequestrin in human PVs increase with age but decrease by ~30% with AF, suggesting impaired calcium handling abilities may play more significant roles than Pitx2 in the generation of PV triggers of AF. Conclusions: Genetic analysis of Pitx2c expression in PV muscle sleeves and LA tissues of WT and Pitx2cnull+/- mice revealed differential expression patterns. In human PVs, Pitx2 expression shows a regulation pattern with age distinct from that in mice, and genes linked to intracellular calcium handling may play a more important role than Pitx2 in generating trigger foci in PVs to initiate AF.

scholarly journals Paraxial Nodal Expression Reveals a Novel Conserved Structure of the Left-Right Organizer in Four Mammalian Species

2016 ◽  
Vol 201 (2) ◽  
pp. 77-87 ◽  
Author(s):  
Silke S. Schröder ◽  
Nikoloz Tsikolia ◽  
Annette Weizbauer ◽  
Isabelle Hue ◽  
Christoph Viebahn
Keyword(s):  
Histological Analysis ◽  
Mammalian Species ◽  
Model Organism ◽  
Lateral Plate Mesoderm ◽  
Open Surface ◽  
Nodal Domain ◽  
Expression Domain ◽  
Lateral Plate ◽  
Vertebrate Embryo ◽  
Left Right Asymmetry

Nodal activity in the left lateral plate mesoderm is a conserved sign of irreversible left-right asymmetry at early somite stages of the vertebrate embryo. An earlier, paraxial nodal domain accompanies the emergence and initial extension of the notochord and is either left-sided, as in the chick and pig, or symmetrical, as in the mouse and rabbit; intriguingly, this interspecific dichotomy is mirrored by divergent morphological features of the posterior notochord (also known as the left-right organizer), which is ventrally exposed to the yolk sac cavity and carries motile cilia in the latter 2 species only. By introducing the cattle embryo as a new model organism for early left-right patterning, we present data to establish 2 groups of mammals characterized by both the morphology of the left-right organizer and the dynamics of paraxial nodal expression: presence and absence of a ventrally open surface of the early (plate-like) posterior notochord correlates with a symmetrical (in mice and rabbits) versus an asymmetrical (in pigs and cattle) paraxial nodal expression domain next to the notochordal plate. High-resolution histological analysis reveals that the latter domain defines in all 4 mammals a novel ‘parachordal' axial mesoderm compartment, the topography of which changes according to the specific regression of the similarly novel subchordal mesoderm during the initial phases of notochord development. In conclusion, the mammalian axial mesoderm compartment (1) shares critical conserved features despite the marked differences in early notochord morphology and early left-right patterning and (2) provides a dynamic topographical framework for nodal activity as part of the mammalian left-right organizer.

scholarly journals Identification and Analysis of GhEXO Gene Family Indicated That GhEXO7_At Promotes Plant Growth and Development Through Brassinosteroid Signaling in Cotton (Gossypium hirsutum L.)

2021 ◽  
Vol 12 ◽  
Author(s):  
Shengdong Li ◽  
Zhao Liu ◽  
Guoquan Chen ◽  
Ghulam Qanmber ◽  
Lili Lu ◽  
...  
Keyword(s):  
Plant Growth ◽  
Gossypium Hirsutum ◽  
Gene Family ◽  
Growth And Development ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Virus Induced Gene Silencing ◽  
Plant Growth And Development ◽  
Altered Expression ◽  
Protein Motifs

Brassinosteroids (BRs), an efficient plant endogenous hormone, significantly promotes plant nutrient growth adapting to biological and abiotic adversities. BRs mainly promote plant cell elongation by regulating gene expression patterns. EXORDIUM (EXO) genes have been characterized as the indicators of BR response genes. Cotton, an ancient crop, is of great economic value and its fibers can be made into all kinds of fabrics. However, EXO gene family genes have not been full identified in cotton. 175 EXO genes were identified in nine plant species, of which 39 GhEXO genes in Gossypium hirsutum in our study. A phylogenetic analysis grouped all of the proteins encoded by the EXO genes into five major clades. Sequence identification of conserved amino acid residues among monocotyledonous and dicotyledonous species showed a high level of conservation across the N and C terminal regions. Only 25% the GhEXO genes contain introns besides conserved gene structure and protein motifs distribution. The 39 GhEXO genes were unevenly distributed on the 18 At and Dt sub-genome chromosomes. Most of the GhEXO genes were derived from gene duplication events, while only three genes showed evidence of tandem duplication. Homologous locus relationships showed that 15 GhEXO genes are located on collinear blocks and that all orthologous/paralogous gene pairs had Ka > Ks values, indicating purifying selection pressure. The GhEXO genes showed ubiquitous expression in all eight tested cotton tissues and following exposure to three phytohormones, IAA, GA, and BL. Furthermore, GhEXO7_At was mainly expressed in response to BL treatment, and was predominantly expressed in the fibers. GhEXO7_At was found to be a plasma membrane protein, and its ectopic expression in Arabidopsis mediated BR-regulated plant growth and development with altered expression of DWF4, CPD, KCS1, and EXP5. Additionally, the functions of GhEXO7_At were confirmed by virus-induced gene silencing (VIGS) in cotton. This study will provide important genetic resources for future cotton breeding programs.

Expression of achaete-scute homologues in discrete proneural clusters on the developing notum of the medfly Ceratitis capitata, suggests a common origin for the stereotyped bristle patterns of higher Diptera

Development ◽  
2000 ◽  
Vol 127 (7) ◽  
pp. 1411-1420 ◽  
Author(s):  
C. Wulbeck ◽  
P. Simpson
Keyword(s):  
Ceratitis Capitata ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Common Origin ◽  
Regulatory Sequences ◽  
Expression Domain ◽  
Altered Expression ◽  
Spatiotemporal Regulation ◽  
Bristle Patterns ◽  
Bristle Pattern

The stereotyped positioning of sensory bristles in Drosophila has been shown to result from complex spatiotemporal regulation of the proneural achaete-scute genes, that relies on an array of cis-regulatory elements and spatially restricted transcriptional activators such as Pannier. Other species of derived schizophoran Diptera have equally stereotyped, but different, bristle patterns. Divergence of bristle patterns could arise from changes in the expression pattern of proneural genes, resulting from evolution of the cis-regulatory sequences and/or altered expression patterns of transcriptional regulators. Here we describe the isolation of achaete-scute homologues in Ceratitis capitata, a species of acalyptrate Schizophora whose bristle pattern differs slightly from that of Drosophila. At least three genes, scute, lethal of scute and asense have been conserved, thus demonstrating that gene duplication within the achaete-scute complex preceded the separation of the families Drosophilidae and Tephritidae, whose common ancestor goes back more than 100 million years. The expression patterns of these genes provide evidence for conservation of many cis-regulatory elements as well as a common origin for the stereotyped patterns seen on the scutum of many Schizophora. Some aspects of the transcriptional regulation have changed, however, and correlate in the notum with differences in the bristle pattern. The Ceratitis pannier gene was isolated and displays a conserved expression domain in the notum.

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.

Mesendoderm and left-right brain, heart and gut development are differentially regulated by pitx2 isoforms

Development ◽  
2000 ◽  
Vol 127 (5) ◽  
pp. 1081-1093 ◽  
Author(s):  
J.J. Essner ◽  
W.W. Branford ◽  
J. Zhang ◽  
H.J. Yost
Keyword(s):  
Expression Patterns ◽  
Ectopic Expression ◽  
Dorsal Side ◽  
Organ Development ◽  
Gut Development ◽  
Prechordal Plate ◽  
Pitx2 Gene ◽  
Isoform Expression ◽  
Left Right Asymmetry ◽  
Molecular Phenotypes

The pitx2 gene is a member of the bicoid-homeodomain class of transcription factors that has been implicated in the control of left-right asymmetry during organogenesis. Here we demonstrate that in zebrafish there are two pitx2 isoforms, pitx2a and pitx2c, which show distinct expression patterns and have non-overlapping functions during mesendoderm and asymmetric organ development. pitx2c is expressed symmetrically in presumptive mesendoderm during late blastula stages and in the prechordal plate during late gastrulation. pitx2a expression is first detected at bud stage in the anterior prechordal plate. The regulation of early mesendoderm pitx2c expression is dependent on one-eyed pinhead (EGF-CFC-related gene) and spadetail (tbx-transcription factor) and can be induced by ectopic goosecoid expression. Maintenance of pitx2c midline expression is dependent on cyclops (nodal) and schmalspur, but not no tail (brachyury). Ectopic expression of pitx2 isoforms results in distinct morphological and molecular phenotypes, indicating that pitx2a and pitx2c have divergent regulatory functions. Both isoforms downregulate goosecoid on the dorsal side, but in contrast to earlier reports that nodal and lefty are upstream of pitx2, ectopic pitx2c in other regions induces cyclops, lefty2 and goosecoid expression. Asymmetric isoform expression occurs in non-overlapping domains, with pitx2c in left dorsal diencephalon and developing gut and pitx2a in left heart primordium. Targeted asymmetric expression in Xenopus shows that both isoforms can alter left-right development, but pitx2a has a slightly stronger effect on heart laterality. Our results indicate that distinct genetic pathways regulate pitx2a and pitx2c isoform expression, and each isoform regulates different downstream pathways during mesendoderm and asymmetric organ development.

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.

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