A mutation in the zebrafish Na,K‐ATPase subunit <i>atp1a1a.1</i> provides genetic evidence that the sodium potassium pump contributes to left‐right asymmetry downstream or in parallel to nodal flow

Ellertsdóttir, Elín; Ganz, Julia; Dürr, Katrin; Loges, Niki T.; Biemar, Frédéric; Seifert, F.; Ettl, Anne Katrin; Kramer-Zucker, Albrecht; Nitschke, Roland; Driever, Wolfgang

doi:10.1002/dvdy.20800

Cited by 21 publications

(29 citation statements)

References 82 publications

(111 reference statements)

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“…While the details of ion flux usage in the LR pathway of various species differ, H þ and K þ flux roles are conserved to sea urchin and Ciona (Duboc et al, 2005;Hibino et al, 2006;Shimeld and Levin, 2006). In the zebrafish, the (Kawakami et al, 2005;Adams et al, 2006) and Na þ / K þ -ATPase (Ellertsdottir et al, 2006) are also known to be important for normal asymmetry, but no asymmetric localization has yet been reported. Rhythmic Ca þþ waves have been described during fish gastrulation (Gilland et al, 1999), consistent with the calcium fluxes discovered in mice and chick Raya et al, 2004), although the connection to downstream LR markers is not yet characterized.…”

Section: Evolutionary Conservation 2: Which Of the Known Mechanisms Amentioning

confidence: 94%

Is the early left‐right axis like a plant, a kidney, or a neuron? The integration of physiological signals in embryonic asymmetry

Levin¹

2006

Birth Defects Research Pt C

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Embryonic morphogenesis occurs along three orthogonal axes. While the patterning of the anterior-posterior and dorsal-ventral axes has been increasingly well-characterized, the left-right (LR) axis has only relatively recently begun to be understood at the molecular level. The mechanisms that ensure invariant LR asymmetry of the heart, viscera, and brain involve fundamental aspects of cell biology, biophysics, and evolutionary biology, and are important not only for basic science but also for the biomedicine of a wide range of birth defects and human genetic syndromes. The LR axis links biomolecular chirality to embryonic development and ultimately to behavior and cognition, revealing feedback loops and conserved functional modules occurring as widely as plants and mammals. This review focuses on the unique and fascinating physiological aspects of LR patterning in a number of vertebrate and invertebrate species, discusses several profound mechanistic analogies between biological regulation in diverse systems (specifically proposing a nonciliary parallel between kidney cells and the LR axis based on subcellular regulation of ion transporter targeting), highlights the possible importance of early, highly-conserved intracellular events that are magnified to embryo-wide scales, and lays out the most important open questions about the function, evolutionary origin, and conservation of mechanisms underlying embryonic asymmetry.

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Section: Evolutionary Conservation 2: Which Of the Known Mechanisms Amentioning

confidence: 94%

Is the early left‐right axis like a plant, a kidney, or a neuron? The integration of physiological signals in embryonic asymmetry

Levin¹

2006

Birth Defects Research Pt C

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“…Whole Mount in Situ Hybridization, Section, and Immunostaining-One-color whole mount in situ hybridization was performed as previously described (26), using established antisense probes (4,21,22,27,28).…”

Section: Methodsmentioning

confidence: 99%

Retinoic Acid Signaling Sequentially Controls Visceral and Heart Laterality in Zebrafish

Huang

Liu

et al. 2011

Journal of Biological Chemistry

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During zebrafish development, the left-right (LR) asymmetric signals are first established around the Kupffer vesicle (KV), a ciliated organ generating directional fluid flow. Then, LR asymmetry is conveyed and stabilized in the lateral plate mesoderm. Although numerous molecules and signaling pathways are involved in controlling LR asymmetry, mechanistic difference and concordance between different organs during LR patterning are poorly understood. Here we show that RA signaling regulates laterality decisions at two stages in zebrafish. Before the 2-somite stage (2So), inhibition of RA signaling leads to randomized visceral laterality through bilateral expression of nodal/spaw in the lateral plate mesoderm, which is mediated by increases in cilia length and defective directional fluid flow in KV. Fgf8 is required for the regulation of cilia length by RA signaling. Blockage of RA signaling before 2So also leads to mild defects of heart laterality, which become much more severe through perturbation of cardiac bmp4 asymmetry when RA signaling is blocked after 2So. At this stage, visceral laterality and the left-sided Nodal remain unaffected. These findings suggest that RA signaling controls visceral laterality through the leftsided Nodal signal before 2So, and regulates heart laterality through cardiac bmp4 mainly after 2So, first identifying sequential control and concordance of visceral and heart laterality.

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“…This is thought to cause an asymmetric calcium signal that establishes the left and right body axis. However, it should be noted that several other models have been put forth to explain the role of cilia in establishing the body axis and that true mechanisms have not yet been firmly established (93,94).…”

Section: Cilia and The Extrarenal Pathologies That Are Associated Witmentioning

confidence: 99%

Role of Primary Cilia in the Pathogenesis of Polycystic Kidney Disease

Yoder¹

2007

Journal of the American Society of Nephrology

257

219

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Cysts in the kidney are among the most common inherited human pathologies, and recent research has uncovered that a defect in cilia-mediated signaling activity is a key factor that leads to cyst formation. The cilium is a microtubule-based organelle that is found on most cells in the mammalian body. Multiple proteins whose functions are disrupted in cystic diseases have now been localized to the cilium or at the basal body at the base of the cilium. Current data indicate that the cilium can function as a mechanosensor to detect fluid flow through the lumen of renal tubules. Flow-mediated deflection of the cilia axoneme induces an increase in intracellular calcium and alters gene expression. Alternatively, a recent finding has revealed that the intraflagellar transport 88/polaris protein, which is required for cilia assembly, has an additional role in regulating cell-cycle progression independent of its function in ciliogenesis. Further research directed at understanding the relationship between the cilium, cell-cycle, and cilia-mediated mechanosensation and signaling activity will hopefully provide important insights into the mechanisms of renal cyst pathogenesis and lead to better approaches for therapeutic intervention.

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A mutation in the zebrafish Na,K‐ATPase subunit atp1a1a.1 provides genetic evidence that the sodium potassium pump contributes to left‐right asymmetry downstream or in parallel to nodal flow

Cited by 21 publications

References 82 publications

Is the early left‐right axis like a plant, a kidney, or a neuron? The integration of physiological signals in embryonic asymmetry

Is the early left‐right axis like a plant, a kidney, or a neuron? The integration of physiological signals in embryonic asymmetry

Retinoic Acid Signaling Sequentially Controls Visceral and Heart Laterality in Zebrafish

Role of Primary Cilia in the Pathogenesis of Polycystic Kidney Disease

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