Classification of left-right patterning defects in zebrafish, mice, and humans

Bisgrove, Brent W.; Yost, H. Joseph

doi:10.1002/ajmg.1180

Cited by 49 publications

(48 citation statements)

References 102 publications

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“…The bilateral expression of both genes might be explained by an impaired midline structure. This has been shown for several mutants in mouse and zebrafish (Bisgrove and Yost, 2001). However, this does not explain why the percentage of mutants with bilateral expression of Pitx2 was higher than with bilateral expression of Nodal.…”

Section: Discussionsupporting

confidence: 56%

“…A complex regulatory network of genes required for the initiation, formation and maintenance of LR asymmetry of vertebrates has been discovered (Bisgrove and Yost, 2001;Capdevila et al, 2000;Hamada et al, 2002;Wood, 1997). The TGFβ family genes Nodal and Leftb, which are the earliest asymmetrically expressed genes in mouse described so far, play pivotal roles in this process.…”

Section: Discussionmentioning

confidence: 99%

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Node and midline defects are associated with left-right development inDelta1mutant embryos

Przemeck¹,

Heinzmann²,

Beckers³

et al. 2003

Development

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Axes formation is a fundamental process of early embryonic development. In addition to the anteroposterior and dorsoventral axes, the determination of the left-right axis is crucial for the proper morphogenesis of internal organs and is evolutionarily conserved in vertebrates. Genes known to be required for the normal establishment and/or maintenance of left-right asymmetry in vertebrates include, for example, components of the TGF-β family of intercellular signalling molecules and genes required for node and midline function. We report that Notch signalling, which previously had not been implicated in this morphogenetic process, is required for normal left-right determination in mice. We show, that the loss-of-function of the delta 1 (Dll1) gene causes a situs ambiguous phenotype, including randomisation of the direction of heart looping and embryonic turning. The most probable cause for this left-right defect in Dll1 mutant embryos is a failure in the development of proper midline structures. These originate from the node, which is disrupted and deformed in Dll1 mutant embryos. Based on expression analysis in wild-type and mutant embryos, we suggest a model, in which Notch signalling is required for the proper differentiation of node cells and node morphology.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Node and midline defects are associated with left-right development inDelta1mutant embryos

Przemeck¹,

Heinzmann²,

Beckers³

et al. 2003

Development

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“…Evidence accumulated over the past decade has delineated a conserved cascade of molecular asymmetries, including nodal, lefty1 (lft1), lefty2 (lft2) and pitx2, in the lateral plate mesoderm (LPM). Disruption of the asymmetric expression pattern of these laterality genes causes abnormalities in the LR morphogenesis of the brain, heart and visceral organs in mouse, chick, frog and zebrafish (for reviews, see Burdine and Schier, 2000;Capdevila et al, 2000;Bisgrove and Yost, 2001).…”

Section: Introductionmentioning

confidence: 99%

Na,K-ATPase α2 and Ncx4a regulate zebrafish left-right patterning

et al. 2007

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A conserved molecular cascade involving Nodal signaling that patterns the laterality of the lateral mesoderm in vertebrates has been extensively studied, but processes involved in the initial break of left-right (LR) symmetry are just beginning to be explored. Here we report that Na,K-ATPase ␣2 and Ncx4a function upstream of Nodal signaling to regulate LR patterning in zebrafish. Knocking down Na,K-ATPase ␣2 and Ncx4a activity in dorsal forerunner cells (DFCs), which are precursors of Kupffer's vesicle (KV), is sufficient to disrupt asymmetric gene expression in the lateral plate mesoderm and randomize the placement of internal organs, indicating that the activity of Na,K-ATPase ␣2 and Ncx4a in DFCs/KV is crucial for LR patterning. High-speed videomicroscopy and bead implantation experiments show that KV cilia are immobile and the directional fluid flow in KV is abolished in Na,K-ATPase ␣2 and Ncx4a morphants, suggesting their essential role in KV ciliary function. Furthermore, we found that intracellular Ca 2+ levels are elevated in Na,K-ATPase ␣2 and Ncx4a morphants and that the defects in ciliary motility, KV fluid flow and placement of internal organs induced by their knockdown could be suppressed by inhibiting the activity of Ca 2+ /calmodulin-dependent protein kinase II. Together, our data demonstrate that Na,K-ATPase ␣2 and Ncx4a regulate LR patterning by modulating intracellular calcium levels in KV and by influencing cilia function, revealing a previously unrecognized role for calcium signaling in LR patterning.

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“…Several zebrafish "looping" mutants have been isolated and many of these mutants have alterations in the positioning of other organs as well as the heart; mutants that have aberrations in the establishment of midline structures, such as the notochord in no tail (ntl), floating head (flh), and momo (mom), or the floor plate as in cyclops (cyc/ndr2) display randomized heart looping Halpern et al, 1997;Rebagliati et al, 1998;Sampath et al, 1998;Bisgrove et al, 2000;Amacher et al, 2002). The development of the notochord and the floor plate are hypothesized to act at the midline as molecular barriers that prevent the dispersion of asymmetrical signals (Bisgrove and Yost, 2001). In humans and zebrafish, left-sided Nodal signaling is thought to be critical for determining the left-right axis.…”

Section: Heart-looping and Laterality Defectsmentioning

confidence: 99%

Modeling human hematopoietic and cardiovascular diseases in zebrafish

North

Zon

2003

Developmental Dynamics

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Zebrafish have emerged as a useful vertebrate model system in which unbiased large-scale screens have revealed hundreds of mutations affecting vertebrate development. Many zebrafish mutants closely resemble known human disorders, thus providing intriguing prospects for uncovering the genetic basis of human diseases and for the development of pharmacologic agents that inhibit or correct the progression of developmental disorders. The rapid pace of advances in genomic sequencing and map construction, in addition to morpholino targeting and transgenic techniques, have facilitated the identification and analysis of genes associated with zebrafish mutants, thus promoting the development of zebrafish as a model for human disorders. This review aims to illustrate how the zebrafish has been used to identify unknown genes, to assign function to known genes, and to delineate genetic pathways, all contributing valuable leads toward understanding human pathophysiology. Developmental Dynamics 228:568 -583, 2003.

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Classification of left-right patterning defects in zebrafish, mice, and humans

Cited by 49 publications

References 102 publications

Node and midline defects are associated with left-right development inDelta1mutant embryos

Node and midline defects are associated with left-right development inDelta1mutant embryos

Na,K-ATPase α2 and Ncx4a regulate zebrafish left-right patterning

Modeling human hematopoietic and cardiovascular diseases in zebrafish

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