Patterning the heart's left-right axis: From zebrafish to man

Goldstein, Allan M.; Ticho, Baruch S.; Fishman, Mark C.

doi:10.1002/(sici)1520-6408(1998)22:3<278::aid-dvg9>3.0.co;2-3

Cited by 22 publications

(11 citation statements)

References 47 publications

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“…In particular, children born with severe heterotaxia generally die shortly after birth, usually due to severe cardiac defects. In many cases, laterality defects in humans that result in heterotaxia can be classified into two primary categories: right isomerism associated with asplenia/hyposplenia and, conversely, left isomerism associated with polysplenia (Goldstein et al 1998;Kosaki and Casey 1998). Our studies show that Cryptic mutant mice recapitulate many features of the right isomerism/asplenia syndrome, suggesting that the Cryptic mutant mice may represent a model for a major category of human L-R laterality defects.…”

Section: Cryptic Mutants As a Model For Right Isomerism/ Asplenia Synmentioning

confidence: 99%

Conserved requirement for EGF-CFC genes in vertebrate left-right axis formation

Yan¹,

Gritsman

Ding

et al. 1999

Genes & Development

229

218

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Specification of the left-right (L-R) axis in the vertebrate embryo requires transfer of positional informationfrom the node to the periphery, resulting in asymmetric gene expression in the lateral plate mesoderm. We show that this activation of L-R lateral asymmetry requires the evolutionarily conserved activity of members of the EGF-CFC family of extracellular factors. Targeted disruption of murine Cryptic results in L-R laterality defects including randomization of abdominal situs, hyposplenia, and pulmonary right isomerism, as well as randomized embryo turning and cardiac looping. Similarly, zebrafish one-eyed pinhead (oep) mutants that have been rescued partially by mRNA injection display heterotaxia, including randomization of heart looping and pancreas location. In both Cryptic and oep mutant embryos, L-R asymmetric expression of Nodal/cyclops, Lefty2/antivin, and Pitx2 does not occur in the lateral plate mesoderm, while in Cryptic mutants Lefty1 expression is absent from the prospective floor plate. Notably, L-R asymmetric expression of Nodal at the lateral edges of the node is still observed in Cryptic mutants, indicating that L-R specification has occurred in the node but not the lateral plate. Combined with the previous finding that oep is required for nodal signaling in zebrafish, we propose that a signaling pathway mediated by Nodal and EGF-CFC activities is essential for transfer of L-R positional information from the node.

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Section: Cryptic Mutants As a Model For Right Isomerism/ Asplenia Synmentioning

confidence: 99%

Conserved requirement for EGF-CFC genes in vertebrate left-right axis formation

Yan¹,

Gritsman

Ding

et al. 1999

Genes & Development

229

218

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“…The remaining expression of Shh on the left is responsible for inducing nodal on the left, ultimately specifying heart situs. When twins arise from two parallel primitive streaks, the activin produced on the right side of the left embryo may inhibit the expression of SHH in the left side of the right embryo [Goldstein et al, 1998] (Fig. 16).…”

Section: Clinical Reportsmentioning

confidence: 99%

Conjoined twins: Morphogenesis of the heart and a review

Gilbert‐Barness¹,

Debich-Spicer²,

Opitz³

2003

American J of Med Genetics Pt A

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Five cases of conjoined twins have been studied. These included three thoracopagus twins, one monocephalus diprosopus (prosop = face), and one dicephalus dipus dibrachus. The thoracopagus twins were conjoined only from the upper thorax to the umbilicus with a normal foregut. These three cases shared a single complex multiventricular heart, one with a four chambered heart with one atrium and one ventricle belonging to each twin with complex venous and arterial connection; two had a seven chambered heart with four atria and three ventricles. The mono-cephalus diprosopus twins had a single heart with tetralogy of Fallot. The dicephalus twins had two separate axial skeletons to the sacrum, two separate hearts were connected between the right atria with a shared inferior vena cava. Thoracopagus twinning is associated with complex cardiac malformations. The cardiac anlagen in cephalopagus or diprosopus are diverted and divided along with the entire rostral end of the embryonic disc and result in two relatively normal shared hearts. However, in thoracopagus twins the single heart is multiventricular and suggests very early union with fusion of the cardiac anlagen before significant differentiation. Cardiac morphogenesis in conjoined twins therefore appears to depend on the site of the conjoined fusion and the temporal and spatial influence that determines morphogenesis as well as abnormally oriented embryonic axes.

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“…Candidate #1 encodes ribophorin I, a subunit of oligosaccharyltransferase (Kelleher et al 1992), candidate #14 encodes protein disulfide isomerase-related protein p5 (see text), candidate #18 encodes chorein, a gene responsible for choera-acanthocytosis (Rampoldi et al 2001;Ueno et al 2001), and candidate #20 has weak homology to yeast tf2-transposon. monly associated with heterotaxy (Goldstein et al 1998;Kosaki and Casey 1998;Bisgrove and Yost 2001), we analyzed the development of additional organ systems in PDI-P5-depleted embryos. The pancreas and liver, which can be detected by virtue of expression of the preproinsulin and gata-6 genes, respectively, are both situated asymmetrically in most WT embryos-the pancreas to the right of the midline, and the liver to the left of the midline (Fig.…”

Section: Asymmetric Morphogenesis and Laterality Patterning Requires mentioning

confidence: 99%

“…Both asymmetric gene expression and subsequent asymmetric morphogenetic processes are regulated by the embryonic midline (Goldstein et al 1998;Yost 1998;Roessler and Muenke 2001). Surgical removal of midline tissues in chick, Xenopus, or zebrafish (Danos and Yost 1996;Lohr et al 1997;Concha et al 2000) or deletion of midline tissues in embryonic zebrafish or mouse mutants (Danos and Yost 1996;Chen et al 1997;Dufort et al 1998;King et al 1998;Melloy et al 1998;Izraeli et al 1999;Bisgrove et al 2000;Chin et al 2000) leads to bilateral expression of nodal, lefty, and pitx2 and produces laterality defects in the formation of the heart, gut, and brain.…”

mentioning

confidence: 99%

A protein disulfide isomerase expressed in the embryonic midline is required for left/right asymmetries

2002

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Although the vertebrate embryonic midline plays a critical role in determining the left/right asymmetric development of multiple organs, few genes expressed in the midline are known to function specifically in establishing laterality patterning. Here we show that a gene encoding protein disulfide isomerase P5 (PDI-P5) is expressed at high levels in the organizer and axial mesoderm and is required for establishing left/right asymmetries in the zebrafish embryo. pdi-p5 was discovered in a screen to detect genes down-regulated in the zebrafish midline mutant one-eyed pinhead and expressed predominantly in midline tissues of wild-type embryos. Depletion of the pdi-p5 product with morpholino antisense oligonucleotides results in loss of the asymmetric development of the heart, liver, pancreas, and gut. In addition, PDI-P5 depletion results in bilateral expression of all genes known to be expressed asymmetrically in the lateral plate mesoderm and the brain during embryogenesis. The laterality defects caused by pdi-p5 antisense treatment arise solely due to loss of the PDI-P5 protein, as they are reversed when treated embryos are supplied with an exogenous source of the PDI-P5 protein. Thus the spectrum of laterality defects resulting from depletion of the PDI-P5 protein fully recapitulates that resulting from loss of the midline. As loss of PDI-P5 does not appear to interfere with other aspects of midline development or function, we propose that PDI-P5 is specifically involved in the production of midline-derived signals required to establish left/right asymmetry.

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Patterning the heart's left-right axis: From zebrafish to man

Cited by 22 publications

References 47 publications

Conserved requirement for EGF-CFC genes in vertebrate left-right axis formation

Conserved requirement for EGF-CFC genes in vertebrate left-right axis formation

Conjoined twins: Morphogenesis of the heart and a review

A protein disulfide isomerase expressed in the embryonic midline is required for left/right asymmetries

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