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

Levin, Michael

doi:10.1002/bdrc.20078

Cited by 64 publications

(100 citation statements)

References 484 publications

(445 reference statements)

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“…To select studies for analysis, PubMed was searched with keywords “left right asymmetry.” Additional studies were found from citation lists at the end of comprehensive review articles (Hirokawa et al, 2006; Levin, 2005; 2006; 2007; Levin and Palmer, 2007; Shiratori and Hamada, 2006). Any study that examined the effects of a genetic mutation, molecular manipulation (morpholino treatment, injection of mRNA, etc.…”

Section: Methodsmentioning

confidence: 99%

“…kinesin and LRD (Qiu et al, 2005)] and cell polarity proteins (Bunney et al, 2003a). Because of their LR-biased localizations, these motor and polarity proteins distribute ion transporters in a biased manner between the early blastomeres (Levin, 2006); the asymmetrically distributed cargo includes two proton pumps (Levin et al, 2002; Adams et al, 2006) and two potassium channels (Aw et al, 2008; Morokuma et al, 2008b). Coupled with a network of open gap junctions, the pH gradients and differences in membrane voltage that result from the biased localization of these ion transporters allow charged molecules such as serotonin to be distributed to the right- and ventral-most blastomere (Fukumoto et al, 2005a; Fukumoto et al, 2005b).…”

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: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Laterality defects are influenced by timing of treatments and animal model

Vandenberg

2012

Differentiation

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“…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%

“…The asymmetric fluxes and transmembrane potential gradients resulting from the biased localization of these transporters, together with a network of open gap junctions, allows LR morphogens such as serotonin to be distributed to the right-and ventral-most blastomere (Fukumoto et al, 2005a,b). All of these steps are required for asymmetry of subsequent gene expression and organ situs (Levin, 2006). While this scheme has been studied in most detail in Xenopus embryos, analysis of a wide variety of phyla reveals surprising conservation in the pathways involved (Levin, 2006;Oviedo and Levin, 2007).…”

Section: Introductionmentioning

confidence: 99%

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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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Molecular clocks underlying vertebrate embryo segmentation: A 10‐year‐old hairy‐go‐round

Andrade

Palmeirim

Bajanca

2007

Birth Defects Research Pt C

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Segmentation of the vertebrate embryo body is a fundamental developmental process that occurs with strict temporal precision. Temporal control of this process is achieved through molecular segmentation clocks, evidenced by oscillations of gene expression in the unsegmented presomitic mesoderm (PSM, precursor tissue of the axial skeleton) and in the distal limb mesenchyme (limb chondrogenic precursor cells). The first segmentation clock gene, hairy1, was identified in the chick embryo PSM in 1997. Ten years later, chick hairy2 expression unveils a molecular clock operating during limb development. This review revisits vertebrate embryo segmentation with special emphasis on the current knowledge on somitogenesis and limb molecular clocks. A compilation of human congenital disorders that may arise from deregulated embryo clock mechanisms is presented here, in an attempt to reconcile different sources of information regarding vertebrate embryo development. Challenging open questions concerning the somitogenesis clock are presented and discussed, such as When?, Where?, How?, and What for? Hopefully the next decade will be equally rich in answers.

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

Cited by 64 publications

References 484 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

Molecular clocks underlying vertebrate embryo segmentation: A 10‐year‐old hairy‐go‐round

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