Zic3 is involved in the left-right specification of the Xenopus embryo

Development ◽  
2000 ◽  
Vol 127 (22) ◽  
pp. 4787-4795 ◽  
Author(s):  
T. Kitaguchi ◽  
T. Nagai ◽  
K. Nakata ◽  
J. Aruga ◽  
K. Mikoshiba
Keyword(s):  
Molecular Basis ◽  
Xenopus Embryo ◽  
Zinc Finger Domain ◽  
Lateral Plate Mesoderm ◽  
Vertebrate Development ◽  
Gastrula Stage ◽  
Lateral Plate ◽  
The Right ◽  
Early Gastrula ◽  
Pitx2 Expression

Establishment of left-right (L-R) asymmetry is fundamental to vertebrate development. Several genes involved in L-R asymmetry have been described. In the Xenopus embryo, Vg1/activin signals are implicated upstream of asymmetric nodal related 1 (Xnr1) and Pitx2 expression in L-R patterning. We report here that Zic3 carries the left-sided signal from the initial activin-like signal to determinative factors such as Pitx2. Overexpression of Zic3 on the right side of the embryo altered the orientation of heart and gut looping, concomitant with disturbed laterality of expression of Xnr1 and Pitx2, both of which are normally expressed in the left lateral plate mesoderm. The results indicate that Zic3 participates in the left-sided signaling upstream of Xnr1 and Pitx2. At early gastrula, Zic3 was expressed not only in presumptive neuroectoderm but also in mesoderm. Correspondingly, overexpression of Zic3 was effective in the L-R specification at the early gastrula stage, as revealed by a hormone-inducible Zic3 construct. The Zic3 expression in the mesoderm is induced by activin (beta) or Vg1, which are also involved in the left-sided signal in L-R specification. These findings suggest that an activin-like signal is a potent upstream activator of Zic3 that establishes the L-R axis. Furthermore, overexpression of the zinc-finger domain of Zic3 on the right side is sufficient to disturb the L-R axis, while overexpression of the N-terminal domain on the left side affects the laterality. These results suggest that Zic3 has at least two functionally important domains that play different roles and provide a molecular basis for human heterotaxy, which is an L-R pattern anomaly caused by a mutation in human ZIC3.

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.

Hindlimb patterning and mandible development require the Ptx1 gene

Development ◽  
1999 ◽  
Vol 126 (9) ◽  
pp. 1805-1810 ◽  
Author(s):  
C. Lanctot ◽  
A. Moreau ◽  
M. Chamberland ◽  
M.L. Tremblay ◽  
J. Drouin
Keyword(s):  
Gene Knockout ◽  
Proximal Part ◽  
Branchial Arch ◽  
Dorsal Side ◽  
Lateral Plate Mesoderm ◽  
Lateral Plate ◽  
Similar Time ◽  
The Right ◽  
Tetrapod Evolution

The restricted expression of the Ptx1 (Pitx1) gene in the posterior half of the lateral plate mesoderm has suggested that it may play a role in specification of posterior structures, in particular, specification of hindlimb identity. Ptx1 is also expressed in the most anterior ectoderm, the stomodeum, and in the first branchial arch. Ptx1 expression overlaps with that of Ptx2 in stomodeum and in posterior left lateral plate mesoderm. We now show that targeted inactivation of the mouse Ptx1 gene severely impairs hindlimb development: the ilium and knee cartilage are absent and the long bones are underdeveloped. Greater reduction of the right femur size in Ptx1 null mice suggests partial compensation by Ptx2 on the left side. The similarly sized tibia and fibula of mutant hindlimbs may be taken to resemble forelimb bones: however, the mutant limb buds appear to have retained their molecular identity as assessed by forelimb expression of Tbx5 and by hindlimb expression of Tbx4, even though Tbx4 expression is decreased in Ptx1 null mice. The hindlimb defects appear to be, at least partly, due to abnormal chondrogenesis. Since the most affected structures derive from the dorsal side of hindlimb buds, the data suggest that Ptx1 is responsible for patterning of these dorsal structures and that as such it may control development of hindlimb-specific features. Ptx1 inactivation also leads to loss of bones derived from the proximal part of the mandibular mesenchyme. The dual role of Ptx1 revealed by the gene knockout may reflect features of the mammalian jaw and hindlimbs that were acquired at a similar time during tetrapod evolution.

Progressively restricted expression of a new homeobox-containing gene during Xenopus laevis embryogenesis

Development ◽  
1991 ◽  
Vol 111 (4) ◽  
pp. 1179-1187 ◽  
Author(s):  
M.W. Su ◽  
H.R. Suzuki ◽  
M. Solursh ◽  
F. Ramirez
Keyword(s):  
Mrna Levels ◽  
Gastrula Stage ◽  
Lateral Plate ◽  
Dorsal Neural Tube ◽  
Tailbud Stage ◽  
The Central Nervous System ◽  
Development Levels ◽  
Dorsal Hindbrain ◽  
Early Gastrula

We have isolated cDNAs encoding a novel Xenopus homeodomain-containing protein homologous to the mouse Hox-7.1 and the Drosophila muscle segment homebox (msh). Northern blot and RNAase protection experiments established that transcripts of the frog gene, termed Xhox-7.1, first appear at about the beginning of gastrulation. After a rapid increase, mRNA levels plateau between the neurula and middle-tailbud stages, and decrease steadily thereafter. In situ hybridization localized the Xhox-7.1 message to the dorsal mesodermal mantle of gastrula stage embryos. Comparison of the hybridization patterns of progressively more anterior cross-section of tailbud stage embryos localized the signal to the dorsal neural tube and neural crest, to specific regions of the lateral plate mesoderm, and to the cardiogenic region. By the tadpole stage, the Xhox-7.1 message appears only at specific sites in the central nervous system, such as in the dorsal hindbrain. Thus, during embryonic development levels of Xhox-7.1 expression decrease as the transcript becomes more progressively localized. Finally, evidence is presented of a distinct msh-like transcript (provisionally termed Xhox-7.1′) which begins to accumulate at early-gastrula stage, as well.

scholarly journals Persistent Ventricle Partitioning in the Adult Zebrafish Heart

2021 ◽  
Vol 8 (4) ◽  
pp. 41
Author(s):  
Catherine Pfefferli ◽  
Hannah R. Moran ◽  
Anastasia Felker ◽  
Christian Mosimann ◽  
Anna Jaźwińska
Keyword(s):  
Lateral Plate Mesoderm ◽  
Adult Zebrafish ◽  
Lateral Plate ◽  
Second Heart Field ◽  
Heart Field ◽  
Left And Right ◽  
First Heart Field ◽  
The Right ◽  
Physical Boundary ◽  
Zebrafish Heart

The vertebrate heart integrates cells from the early-differentiating first heart field (FHF) and the later-differentiating second heart field (SHF), both emerging from the lateral plate mesoderm. In mammals, this process forms the basis for the development of the left and right ventricle chambers and subsequent chamber septation. The single ventricle-forming zebrafish heart also integrates FHF and SHF lineages during embryogenesis, yet the contributions of these two myocardial lineages to the adult zebrafish heart remain incompletely understood. Here, we characterize the myocardial labeling of FHF descendants in both the developing and adult zebrafish ventricle. Expanding previous findings, late gastrulation-stage labeling using drl-driven CreERT2 recombinase with a myocardium-specific, myl7-controlled, loxP reporter results in the predominant labeling of FHF-derived outer curvature and the right side of the embryonic ventricle. Raised to adulthood, such lineage-labeled hearts retain broad areas of FHF cardiomyocytes in a region of the ventricle that is positioned at the opposite side to the atrium and encompasses the apex. Our data add to the increasing evidence for a persisting cell-based compartmentalization of the adult zebrafish ventricle even in the absence of any physical boundary.

scholarly journals Transcriptome analysis of regeneration during Xenopus laevis experimental twinning

2019 ◽  
Vol 63 (6-7) ◽  
pp. 301-309
Author(s):  
Eric A. Sosa ◽  
Yuki Moriyama ◽  
Yi Ding ◽  
Nydia Tejeda-Muñoz ◽  
Gabriele Colozza ◽  
...  
Keyword(s):  
Cell Division ◽  
Identical Twins ◽  
Self Organization ◽  
Vertebrate Development ◽  
Rna Seq ◽  
Gastrula Stage ◽  
Sequence Analyses ◽  
Remarkable Property ◽  
Early Gastrula ◽  
Pluripotency Genes

Animal embryos have the remarkable property of self-organization. Over 125 years ago, Hans Driesch separated the two blastomeres of sea urchin embryos and obtained twins, in what was the foundation of experimental embryology. Since then, embryonic twinning has been obtained experimentally in many animals. In a recent study, we developed bisection methods that generate identical twins reliably from Xenopus blastula embryos. In the present study, we have investigated the transcriptome of regenerating half-embryos after sagittal and dorsal-ventral (D-V) bisections. Individual embryos were operated at midblastula (stage 8) with an eyelash hair and cultured until early gastrula (stage 10.5) or late gastrula (stage 12) and the transcriptome of both halves were analyzed by RNA-seq. Since many genes are activated by wound healing in Xenopus embryos, we resorted to stringent sequence analyses and identified genes up-regulated in identical twins but not in either dorsal or ventral fragments. At early gastrula, cell division-related transcripts such as histones were elevated, whereas at late gastrula, pluripotency genes (such as sox2) and germ layer determination genes (such as eomesodermin, ripply2 and activin receptor ACVRI) were identified. Among the down-regulated transcripts, sizzled, a regulator of Chordin stability, was prominent. These findings are consistent with a model in which cell division is required to heal damage, while maintaining pluripotency to allow formation of the organizer with a displacement of 90 0 from its original site. The extensive transcriptomic data presented here provides a valuable resource for data mining of gene expression during early vertebrate development.

BMP2 is a positive regulator of Nodal signaling during left-right axis formation in the chicken embryo

Development ◽  
2002 ◽  
Vol 129 (14) ◽  
pp. 3421-3429
Author(s):  
Thomas Schlange ◽  
Hans-Henning Arnold ◽  
Thomas Brand
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Target Genes ◽  
Bmp Signaling ◽  
Paraxial Mesoderm ◽  
Axis Formation ◽  
Nodal Signaling ◽  
Lateral Plate Mesoderm ◽  
Lateral Plate ◽  
Positive Regulator ◽  
The Right

A model of left-right axis formation in the chick involves inhibition of bone morphogenetic proteins by the antagonist Car as a mechanism of upregulating Nodal in the left lateral plate mesoderm. By contrast, expression of CFC, a competence factor, which is absolutely required for Nodal signaling in the lateral plate mesoderm is dependent on a functional BMP signaling pathway. We have therefore investigated the relationship between BMP and Nodal in further detail. We implanted BMP2 and Noggin-expressing cells into the left lateral plate and paraxial mesoderm and observed a strong upregulation of Nodal and its target genes Pitx2 and Nkx3.2. In addition Cfc, the Nodal type II receptor ActrIIa and Snr were found to depend on BMP signaling for their expression. Comparison of the expression domains of Nodal, Bmp2, Car and Cfc revealed co-expression of Nodal, Cfc and Bmp2, while Car and Nodal only partially overlapped. Ectopic application of BMP2, Nodal, and Car as well as combinations of this signaling molecules to the right lateral plate mesoderm revealed that BMP2 and Car need to synergize in order to specify left identity. We propose a novel model of left-right axis formation, which involves BMP as a positive regulator of Nodal signaling in the chick embryo.

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 Persistent ventricle partitioning in the adult zebrafish heart

2021 ◽  
Author(s):  
Catherine Pfefferli ◽  
Hannah R. Moran ◽  
Anastasia Felker ◽  
Christian Mosimann ◽  
Anna Jazwinska
Keyword(s):  
Lateral Plate Mesoderm ◽  
Adult Zebrafish ◽  
Lateral Plate ◽  
Second Heart Field ◽  
Heart Field ◽  
Left And Right ◽  
First Heart Field ◽  
The Right ◽  
Physical Boundary ◽  
Zebrafish Heart

The vertebrate heart integrates cells from the early-differentiating first heart field (FHF) and the later-differentiating second heart field (SHF) emerging from the lateral plate mesoderm. In mammals, this process forms the basis for the development of the left and right ventricle chambers and subsequent chamber septation. The single ventricle-forming zebrafish heart also integrates FHF and SHF lineages during embryogenesis, yet the contributions of these two myocardial lineages to the adult zebrafish heart remain incompletely understood. Here, we characterize the myocardial labeling of FHF descendants in both the developing and adult zebrafish ventricle. Expanding previous findings, late gastrulation-stage labeling using drl-driven CreERT2 recombinase with a myocardium-specific, myl7-controlled loxP reporter results in predominant labeling of FHF-derived outer curvature and the right side of the embryonic ventricle. Raised to adulthood, such lineage-labeled hearts retain broad areas of FHF cardiomyocytes in a region of the ventricle that is positioned at the opposite side to the atrium and encompasses the apex. Our data add to the increasing evidence for a persisting cell-based compartmentalization of the adult zebrafish ventricle even in the absence of any physical boundary.

Functional differences among Xenopus nodal-related genes in left-right axis determination

Development ◽  
1997 ◽  
Vol 124 (17) ◽  
pp. 3293-3302 ◽  
Author(s):  
K. Sampath ◽  
A.M. Cheng ◽  
A. Frisch ◽  
C.V. Wright
Keyword(s):  
Causative Factor ◽  
Lateral Plate Mesoderm ◽  
Lateral Plate ◽  
Functional Differences ◽  
Evolutionarily Conserved ◽  
Dorsal Mesoderm ◽  
Hedgehog Proteins ◽  
Vertebrate Embryos ◽  
The Right

An association has been noted previously in chick, mouse and frog embryos between asymmetric nodal-related gene expression and embryonic situs, implying an evolutionarily conserved role in left-right specification. Of the four Xenopus nodal-related genes expressed during gastrulation, only Xnr-1 is re-expressed unilaterally in the left lateral plate mesoderm at neurula/tailbud stages. Here, we show that the asymmetric expression of Xnr-1 can be made bilaterally symmetric by right-sided microinjection of RNA encoding active Xenopus hedgehog proteins. Moreover, we provide the first evidence that Xnr-1 expression per se is a causal factor in left-right axis determination. When plasmids expressing Xnr-1 were delivered unilaterally to the right side of Xenopus embryos, a reversed laterality of both the heart and gut (homotaxic reversal) was induced in 40% of surviving embryos, while an additional 10–20% showed reversal of the heart or gut alone (heterotaxia). This effect on laterality was specific to Xnr-1, since neither Xnr-2 nor Xnr-3 plasmids had this activity. In addition, we find that Xnr-1 and Xnr-2, which have both been defined as mesoderm inducers from overexpression studies, show quantitative differences in their ability to induce dorsal mesoderm. Together, these findings suggest that the various Xnrs perform substantially different functions during Xenopus embryogenesis. Moreover, they strongly support the hypothesis that left lateral plate expression of nodal-related genes is a causative factor in the determination of asymmetry in vertebrate embryos.

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