Strategies to establish left/right asymmetry in vertebrates and invertebrates

Spéder, Pauline; Petzoldt, Astrid G.; Suzanne, Magali; Noselli, Stéphane

doi:10.1016/j.gde.2007.05.008

Cited by 93 publications

(94 citation statements)

References 69 publications

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“…Additionally, some phenotypes, such as heterotaxia, are quite detrimental to the health of humans and mammals, as evidenced by perinatal lethality of heterotaxic mutants [for example, (Tan et al, 2007)], while heterotaxic tadpoles appear quite healthy and can live for several months (Morokuma et al, 2008a). These observations suggest that there may be some fundamental differences in how animals with very different embryonic architectures establish LR asymmetry (Speder et al, 2007; Palmer, 2004). …”

Section: Introductionmentioning

confidence: 95%

“…The second point is that most studies exploring the role of cilia in the process of symmetry breaking have relied on fish (zebrafish and medaka) and mice to generate data, while studies exploring earlier mechanisms typically use Xenopus and chick (Figure 1). Fish, frogs, mice and chick may establish the LR axis at different times with differently shaped body plans (Hackett, 2002; Speder et al, 2007), yet studies rarely look at any particular mechanism of generating LR asymmetry across species. It is important to understand whether the choice of animal model itself influences the conclusions that are made about the mechanisms involved in LR patterning.…”

Section: Introductionmentioning

confidence: 99%

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Laterality defects are influenced by timing of treatments and animal model

Vandenberg

2012

Differentiation

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The timing of when the embryonic left-right (LR) axis is first established and the mechanisms driving this process are subjects of strong debate. While groups have focused on the role of cilia in establishing the LR axis during gastrula and neurula stages, many animals appear to orient the LR axis prior to the appearance of, or without the benefit of, motile cilia. Because of the large amount of data available in the published literature and the similarities in the type of data collected across labs, I have examined relationships between the studies that do and do not implicate cilia, the choice of animal model, the kinds of LR patterning defects observed, and the penetrance of LR phenotypes. I found that treatments affecting cilia structure and motility had a higher penetrance for both altered gene expression and improper organ placement compared to treatments that affect processes in early cleavage stage embryos. I also found differences in penetrance that could be attributed to the animal models used; the mouse is highly prone to LR randomization. Additionally, the data were examined to address whether gene expression can be used to predict randomized organ placement. Using regression analysis, gene expression was found to be predictive of organ placement in frogs, but much less so in the other animals examined. Together, these results challenge previous ideas about the conservation of LR mechanisms, with the mouse model being significantly different from fish, frogs and chick in almost every aspect examined. Additionally, this analysis indicates that there may be missing pieces in the molecular pathways that dictate how genetic information becomes organ positional information in vertebrates; these gaps will be important for future studies to identify, as LR asymmetry is not only a fundamentally fascinating aspect of development but also of considerable biomedical importance.

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Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Laterality defects are influenced by timing of treatments and animal model

Vandenberg

2012

Differentiation

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“…In the past 2 decades, significant progress has been made in understanding the genetic pathways that result in the specific arrangement and morphogenesis of the heart, viscera, and brain of vertebrate and invertebrate model systems (Levin, 2005;Speder et al, 2007). In particular, extensive cascades of asymmetric gene expression have been described that ultimately…”

Section: Introductionmentioning

confidence: 99%

“…Other active areas of investigation include the asymmetric morphogenesis of the organs (Kurpios et al, 2008), the asymmetry of the brain and central nervous system (Sun and Walsh, 2006;Sagasti, 2007;Taylor et al, 2010), the conservation of asymmetry mechanisms throughout phyla (Levin, 2006;Speder et al, 2007;Raya and Izpisua Belmonte, 2008), and various curious presentations of asymmetry in the health and disease of human patients that are not easily dissected in tractable model systems .…”

Section: Introductionmentioning

confidence: 99%

Far from solved: A perspective on what we know about early mechanisms of left–right asymmetry

Vandenberg

Levin

2010

Developmental Dynamics

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Consistent laterality is a crucial aspect of embryonic development, physiology, and behavior. While strides have been made in understanding unilaterally expressed genes and the asymmetries of organogenesis, early mechanisms are still poorly understood. One popular model centers on the structure and function of motile cilia and subsequent chiral extracellular fluid flow during gastrulation. Alternative models focus on intracellular roles of the cytoskeleton in driving asymmetries of physiological signals or asymmetric chromatid segregation, at much earlier stages. All three models trace the origin of asymmetry back to the chirality of cytoskeletal organizing centers, but significant controversy exists about how this intracellular chirality is amplified onto cell fields. Analysis of specific predictions of each model and crucial recent data on new mutants suggest that ciliary function may not be a broadly conserved, initiating event in left-right patterning. Many questions about embryonic left-right asymmetry remain open, offering fascinating avenues for further research in cell, developmental, and evolutionary biology. Developmental Dynamics 239:3131-3146,

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“…Several different mechanisms for l-r (left-right) asymmetry determination have been proposed for vertebrates and invertebrates (Spéder et al, 2007;Vandenberg and Levin, 2009). For examples, in vertebrates, l-r asymmetry is determined by directional nodal flow across the embryonic midline (Nonaka et al, 1998;Nonaka et al, 2002;Blum et al, 2009), whereas in invertebrates such as Drosophila and C. elegans, the actin cytoskeleton and an associated type I myosin, and G-alpha protein regulating spindle orientation seem to be involved, respectively (Hozumi et al, 2006;Spéder et al, 2006;Bergmann et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Spiral cleavages determine the left-right body plan by regulating Nodal pathway in monomorphic gastropods, Physa acuta

Abe¹,

Takahashi²,

Kuroda³

2014

Int. J. Dev. Biol.

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The handedness of gastropods is genetically determined, but the molecular nature of the gene responsible and the associated mechanisms remain unknown. In order to characterize the chiromorphogenesis pathway starting from the gene to the left-right asymmetric body plan, we have closely analyzed the cytoskeletal dynamics of the Physa (P.) acuta embryo, a fresh water non-dimorphic sinistral snail, during the early developmental stage by mechanically altering the handedness of the embryos at the critical spiral third cleavage. A fertile situs inversus was created and the nodal-Pitx gene expression patterns were completely mirror imaged to the wild type at the trochophore stage. Together with our previous work on Lymnaea (L.) stagnalis, we could show that chirality is established at the third cleavage, as dictated by the single handedness-determining gene locus, and then chirality information is transferred via subsequent spiral fourth and fifth cleavages to the later developmental stage, dictating the nodal-Pitx expression pathway. The cytoskeletal dynamics of manipulated and non-manipulated embryos of sinistral P. acuta and dextral dominant L. stagnalis are compared.

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Strategies to establish left/right asymmetry in vertebrates and invertebrates

Cited by 93 publications

References 69 publications

Laterality defects are influenced by timing of treatments and animal model

Laterality defects are influenced by timing of treatments and animal model

Far from solved: A perspective on what we know about early mechanisms of left–right asymmetry

Spiral cleavages determine the left-right body plan by regulating Nodal pathway in monomorphic gastropods, Physa acuta

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