Is left-right asymmetry a form of planar cell polarity?

Aw, Sherry; Levin, Michael

doi:10.1242/dev.015974

Cited by 60 publications

(71 citation statements)

References 109 publications

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“…G,H: Through an as-yet uncharacterized pathway, the localization of morphogens such as serotonin to the right side of the embryo suppresses downstream expression of genes (i.e., Nodal), which are thus expressed only on the left side (G), which eventually leads to asymmetric organ morphogenesis (H). This model can be readily extended to bodyplans where the midline is defined after the initial cleavages are complete by the spread of LR orientation information from coordinator cell(s) by means of planar cell polarity pathways (Aw and Levin, 2009;Vandenberg and Levin, 2010).…”

Section: Cilia and Nodal Flowmentioning

confidence: 99%

“…This pathway has been most clearly elucidated in Xenopus, and involves a system of ion transporters, gap junctions, and serotonergic pathway elements that use electrophoresis to amplify intracellular chirality into multicellular gradients of a small molecule morphogen (Levin and Palmer, 2007;Aw and Levin, 2009). While the MTOC has not yet been molecularly dissected in this role, the other components (i.e., the asymmetric orientation and function of the cytoskeleton, transport proteins, ion transporters, and LR morphogens) are known in significant detail (Fig.…”

Section: Intracellular Mechanisms Origins and Evolution Of Early Cytomentioning

confidence: 99%

“…We recently proposed that the early blastoderm's planar polarization (Wang and Nathans, 2007;Zallen, 2007) also plays a key role in coordinating LR asymmetry (Aw and Levin, 2009;Vandenberg and Levin, 2009). We note that planar cell polarity (PCP) and LR orientation have many similarities, including the need to amplify a patterning signal across large numbers of cells, and the ability of proteins to segregate and orient themselves with respect to each other in a consistently biased manner, generating a large scale signal that originates intracellularly.…”

Section: Amplification: Bioelectric Redistribution Of Morphogens and mentioning

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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Section: Cilia and Nodal Flowmentioning

confidence: 99%

Section: Intracellular Mechanisms Origins and Evolution Of Early Cytomentioning

confidence: 99%

Section: Amplification: Bioelectric Redistribution Of Morphogens and mentioning

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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“…However, "ciliary" proteins, such as left-right dynein, known to be important for LR patterning, also have intracellular roles compatible with cilia-independent functions in laterality (9-12). In contrast to the nodal flow model, we have suggested that asymmetry is instead an ancient, well-conserved property of individual cells arising from the chirality of cytoskeletal structures that is subsequently amplified by physiological mechanisms (4,12,13). Thus, we sought the most evolutionarily distant model systems, and ones that are known not to rely on cilia for LR patterning, to test the hypothesis of fundamental molecular conservation of asymmetry mechanisms.…”

mentioning

confidence: 99%

“…In human beings, abnormalities in the proper development of laterality occur in more than 1 in 8,000 live births and often have significant medical consequences (1). Organ asymmetry is highly conserved among species; however, considerable controversy exists about the early steps of LR patterning among phyla (2)(3)(4) and the physical mechanisms that can break symmetry (5).…”

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confidence: 99%

Early, nonciliary role for microtubule proteins in left–right patterning is conserved across kingdoms

Lobikin

Wang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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104

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Many types of embryos' bodyplans exhibit consistently oriented laterality of the heart, viscera, and brain. Errors of left-right patterning present an important class of human birth defects, and considerable controversy exists about the nature and evolutionary conservation of the molecular mechanisms that allow embryos to reliably orient the left-right axis. Here we show that the same mutations in the cytoskeletal protein tubulin that alter asymmetry in plants also affect very early steps of left-right patterning in nematode and frog embryos, as well as chirality of human cells in culture. In the frog embryo, tubulin α and tubulin γ-associated proteins are required for the differential distribution of maternal proteins to the left or right blastomere at the first cell division. Our data reveal a remarkable molecular conservation of mechanisms initiating left-right asymmetry. The origin of laterality is cytoplasmic, ancient, and highly conserved across kingdoms, a fundamental feature of the cytoskeleton that underlies chirality in cells and multicellular organisms.C. elegans | Xenopus | symmetry breaking C onsistent laterality is a fascinating aspect of embryonic development and has considerable implications for the physiology and behavior of the organism. Although vertebrates are generally bilaterally symmetric externally, most internal organs, such as the heart, viscera, and brain display asymmetric structure and/or unilateral positioning with respect to the left-right (LR) axis. A common defect in LR patterning is the loss of concordance among the sidedness of individual organs known as heterotaxia. In human beings, abnormalities in the proper development of laterality occur in more than 1 in 8,000 live births and often have significant medical consequences (1). Organ asymmetry is highly conserved among species; however, considerable controversy exists about the early steps of LR patterning among phyla (2-4) and the physical mechanisms that can break symmetry (5).One model predicts that cilia-driven extracellular fluid flow during gastrulation is the origin of LR asymmetry (6). Because numerous species initiate asymmetry before (or without) the presence of cilia (7,8), this model implies that asymmetry generation must be poorly conserved, with numerous distinct mechanisms used throughout phyla. However, "ciliary" proteins, such as left-right dynein, known to be important for LR patterning, also have intracellular roles compatible with cilia-independent functions in laterality (9-12). In contrast to the nodal flow model, we have suggested that asymmetry is instead an ancient, well-conserved property of individual cells arising from the chirality of cytoskeletal structures that is subsequently amplified by physiological mechanisms (4,12,13). Thus, we sought the most evolutionarily distant model systems, and ones that are known not to rely on cilia for LR patterning, to test the hypothesis of fundamental molecular conservation of asymmetry mechanisms.Recent findings in Arabidopsis thaliana have shown that mutatio...

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Early Committed Clockwise Cell Chirality Upregulates Adipogenic Differentiation of Mesenchymal Stem Cells

Bao

Chu

et al. 2020

Adv. Biosys.

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determine the LR asymmetry in morphogenesis. [2] For example, chirality has been found in Xenopus egg cortex before fertilization, [1] and can be passed down to more differentiated cells that establish LR body axis of animal body plan, [7] organ distribution, [8-10] and epithelial movement that leads to axial torsion and overall handedness of hindgut. [11,12] For specialized adult cells derived from somatic tissue, footprints of cell chirality can still be seen by their ability of generating cellular torque, [6,13] migration with LR bias, [14-16] or forming specific alignment in the multicellular level. [15,17,18] Through cell-cell communication, the chiral behavior causes LR-biased cell assembly of multicellular structure [15] and regulates permeability of intercellular junctions. [19] Clearly, cell chirality can be manifested in diverse forms and coordinate different morphogenic dynamics, resulting in distinct forms of tissue and organ architecture. Actin cytoskeleton plays an important role in cell chirality. When cultured on micropatterned substrate, the accumulation of actomyosin stress fibers at micropattern boundary is essential to activate the LR bias in cell migration and orientation. [15,17] Molecular studies suggest helical motion of actin filament as the underlying mechanism for the chirality at cellular level. [20,21] Functioning as a built-in machinery, actomyosin cytoskeleton allows chiral nucleus rotation of single cell [21] and generation of cellular torque with rotational bias. [13] Through a series of amplification process, the actin chirality ultimately determines the symmetry breaking in early embryonic development, [1,7,22] cardiac looping, [4,8,23] and organ laterality [9] in vivo. To give rise to such diverse forms of cell chirality, cell differentiation should play a role. [13,15,17] Cell differentiation is a process coupling with chemical [24] and physical factors. [25-27] Based on variation of key proteins in cytoskeleton, [28] cytoskeleton can be changed at early stage of cell differentiation, as shown by upregulation of cytoskeletal contractility [29] and cell morphological features, which can even forecast the cell lineage fate. [28] It suggests that cytoskeletal components, particularly actin, may early respond to the induction of cell differentiation and then actively participate the signal cascades to engage cell fate. Evidences can be found by regulation of cell differentiation via changed cell shape and cell spreading by physical cues [30-38]

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Is left-right asymmetry a form of planar cell polarity?

Cited by 60 publications

References 109 publications

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

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

Early, nonciliary role for microtubule proteins in left–right patterning is conserved across kingdoms

Early Committed Clockwise Cell Chirality Upregulates Adipogenic Differentiation of Mesenchymal Stem Cells

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