Left-right asymmetry

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Left-right asymmetry (LR asymmetry) is the process in early embryonic development that breaks the normal symmetry in the bilateral embryo. In vertebrates, left-right asymmetry is established early in development at a structure called the left-right organizer (the name of which varies between species) and leads to activation of different signalling pathways on the left and right of the embryo. [1] This in turn cause several organs in adults to develop LR asymmetry, such as the tilt of the heart, the different number lung lobes on each side of the body and the position of the stomach and spleen on the right side of the body. [2] If this process does not occur correctly in humans it can result in the syndromes heterotaxy or situs inversus.

Contents

LR asymmetry is pervasive throughout all animals, including invertebrates. Examples of invertebrate LR asymmetry include the large and small claws of the fiddler crab, asymmetrical gut coiling in Drosophila melanogaster, and dextral (clockwise) and sinistral (counterclockwise) coiling of gastropods. This asymmetry can be restricted to a specific organ or feature, as in the crab claws, or be expressed throughout the entire body as in snails.

Developmental basis

Different species have evolved different mechanisms of LR patterning. For example, cilia are critical for LR patterning in many vertebrate species such as humans, rodents, fish and frog, but other species, such as reptiles, birds and pigs develop LR asymmetry without cilia. [3]

Cilia dependent vertebrates

The name of the LR organiser varies between species, and thus includes the node in mice, the gastrocoel roof plate in frog and Kupffer’s vesicle in zebrafish. [4] In each case the LR organizer is found on the dorsal side of the embryo and each organizer cell has a single cilia located on the posterior side of the cell. The combination of location of cells of the dorsal surface combined with the posterior location of the cilia means that when the cilia rotate it creates a left-ward flow across the surface of the organizer. [5] The flow causes loss of Cerl2 and increased Nodal expression on the left side of the organizer, although there is some debate whether this occurs due to a chemical/protein signal or due to the cells physically sensing the flow. [1] In either case, the signal is then transferred to the left Lateral plate mesoderm where it activates a further signalling cascade of genes including Nodal, Pitx2 and Lefty2.

Cilia independent vertebrates

In chickens, LR asymmetry is established at a structure called Hensen’s node. Unlike most other vertebrates, this process is not thought to involve cilia as (i) Hensen’s node does not have motile cilia and (ii) unlike other species, mutations that affect cilia formation do not cause laterality defects in chicken. [6] Instead, chickens establish LR asymmetry through asymmetric cell rearrangements which results in a leftward movement of cells near the Hensen’s node. [7]

Another study has found that pigs do not have cilia within their left right organiser, suggesting pigs also have an alternative cilia independent mechanism for establishing LR asymmetry. [8]

Non-vertebrate deuterostomes

Recently, work has shown that the Nodal-Pitx2 pathway is present and functional in the non-vertebrate deuterostomes (tunicates, sea urchins). [9] [10] In tunicate (ascidian) Ciona intestinalis and Halocynthia roretzi , Nodal is expressed on the left side of the developing embryo and leads to downstream expression of Pitx2. At earlier stages, similar H+/K+ ATPase ion channels are reported to be necessary for correct left-right patterning. [9] While the role of cilia here is still unclear, one study observes that large-scale embryonic movements are required for left-right determination in H. roretzi, and that this movement is possibly achieved through ciliary movements. [11]

In the sea urchin, Nodal is expressed on the right side of the embryo, in contrast to the tunicate and vertebrate condition on the left side. [10] Because protostomes appear to also express Nodal on their right side instead of the left (discussed below), some have suggested that this lends further evidence for the dorsoventral inversion hypothesis. [12]

Protostomes

Ecdysozoa

While D. melanogaster and nematode Caenorhabditis elegans do show left-right asymmetry, the Nodal signaling pathway itself is absent in Ecdysozoa. [12] Instead, cytoskeletal regulators such as Myo31DF, a type ID unconventional myosin, have been found to control left-right asymmetry in organ systems such as genitalia. [13]

Lophotrochozoa

Unlike in Ecdysozoa, the Nodal-Pitx2 pathways have been identified in many lineages within the Lophotrochozoans. [14] When found in brachiopods and molluscs, these genes are asymmetrically expressed on the right. [14] Platyhelminthes, annelids, and nermeteans lack a Nodal orthologue and instead only express Pitx2, which was expressed in association to the nervous system. [14]

Whole body left-right asymmetry in gastropods

Whole body inversion is observed as chiral (dextral, sinistral) coiling in gastropods. While dextral coiling is the most common as it appears in 90-99% of living species, sinistral species still have arisen many times. [15]

Developmental basis of shell coiling

Gastropods undergo spiral cleavage, a feature commonly seen in lophotrochozoans. As the embryo divides, quartets of cells are oriented at angles to each other. In the snail Lymnaea stagnalis, the direction of rotation during the first cell division signals whether the adult will show dextral or sinistral coiling, [16] At the third cleavage (8-cell stage), spindles in dextral snails are inclined clockwise whereas they are counterclockwise in sinistral snails. [17] Furthermore, injecting L. peregra sinistral eggs with the cytoplasm of dextral eggs before the second polar body formation will reverse the polarity of the sinistral embryos. [18] These data show that chirality is heritable and maternally deposited in Lymnaea. [16] [17] [18]

Several studies have begun to investigate the molecular basis of this inheritance. Nodal and Pitx2 are expressed on different sides of the L. stagnalis embryo depending on its chirality – right for dextral, left for sinistral. [19] Downstream of Nodal, decapentaplegic (dpp), shows the same expression pattern. [20] In limpets (gastropods without coiled shells) dpp is expressed symmetrically in Patella vulgata and Nipponacmea fuscoviridis. [20] Additionally, in N. fuscoviridis, dpp has been shown to drive cell proliferation [21]

Upstream of Nodal, Lsdia1/2 have been implicated in controlling L. stagnalis chirality. [22] [23] Davison et al. (2016) mapped the “chirality locus” to a 0.4 Mb region and determined that Lsdia2 is the likely candidate for determining dextral or sinistral coiling. [22] This is a diaphanous-related formin gene involved in cytoskeleton formation. [22] Dextral embryos treated with drugs that inhibited formin activity phenocopied the sinistral condition. Concurrent work from Kuroda et al. (2016) identified the same Lsdia2 gene (called Lsdia1 in their study) but failed to reproduce the formin inhibition results in the Davison et al. study. [23] Additionally, Kuroda et al. (2016) did not find asymmetrically expressed Lsdia2 as was seen in the Davison et al. (2016) study.

See also

Related Research Articles

<span class="mw-page-title-main">Cilium</span> Organelle found on eukaryotic cells

The cilium, is a membrane-bound organelle found on most types of eukaryotic cell. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projection that extends from the surface of the much larger cell body. Eukaryotic flagella found on sperm cells and many protozoans have a similar structure to motile cilia that enables swimming through liquids; they are longer than cilia and have a different undulating motion.

<span class="mw-page-title-main">Situs inversus</span> Condition in which organs are reversed

Situs inversus is a congenital condition in which the major visceral organs are reversed or mirrored from their normal positions. The normal arrangement of internal organs is known as situs solitus. Although cardiac problems are more common, many people with situs inversus have no medical symptoms or complications resulting from the condition, and until the advent of modern medicine, it was usually undiagnosed.

Sinistral and dextral, in some scientific fields, are the two types of chirality ("handedness") or relative direction. The terms are derived from the Latin words for "left" (sinister) and "right" (dexter). Other disciplines use different terms or simply use left and right.

<span class="mw-page-title-main">Symmetry in biology</span> Geometric symmetry in living beings

Symmetry in biology refers to the symmetry observed in organisms, including plants, animals, fungi, and bacteria. External symmetry can be easily seen by just looking at an organism. For example, the face of a human being has a plane of symmetry down its centre, or a pine cone displays a clear symmetrical spiral pattern. Internal features can also show symmetry, for example the tubes in the human body which are cylindrical and have several planes of symmetry.

<span class="mw-page-title-main">Situs solitus</span>

Situs solitus is the medical term referring to the normal position of thoracic and abdominal organs. Anatomically, this means that the heart is on the left with the pulmonary atrium on the right and the systemic atrium on the left along with the cardiac apex. Right-sided organs are the liver, the gall bladder and a trilobed lung as well as the inferior vena cava, while left-sided organs are the stomach, single spleen, a bilobed lung, and the aorta.

Lefty are a class of proteins that are closely related members of the TGF-beta superfamily of growth factors. These proteins are secreted and play a role in left-right asymmetry determination of organ systems during development. Mutations of the genes encoding these proteins have been associated with left-right axis malformations, particularly in the heart and lungs.

The heart is the first functional organ in a vertebrate embryo. There are 5 stages to heart development.

<span class="mw-page-title-main">Gastropod shell</span> Part of the body of a gastropod or snail

The gastropod shell is part of the body of a gastropod or snail, a kind of mollusc. The shell is an exoskeleton, which protects from predators, mechanical damage, and dehydration, but also serves for muscle attachment and calcium storage. Some gastropods appear shell-less (slugs) but may have a remnant within the mantle, or in some cases the shell is reduced such that the body cannot be retracted within it (semi-slug). Some snails also possess an operculum that seals the opening of the shell, known as the aperture, which provides further protection. The study of mollusc shells is known as conchology. The biological study of gastropods, and other molluscs in general, is malacology. Shell morphology terms vary by species group.

<span class="mw-page-title-main">Cerberus (protein)</span> Protein-coding gene in the species Homo sapiens

Cerberus is a protein that in humans is encoded by the CER1 gene. Cerberus is a signaling molecule which contributes to the formation of the head, heart and left-right asymmetry of internal organs. This gene varies slightly from species to species but its overall functions seem to be similar.

<span class="mw-page-title-main">Iwasaki's snail-eater</span> Species of snake

Iwasaki's snail-eater is a species of snake in the family Pareidae. The species is endemic to the Yaeyama Islands in the southern Ryukyu Islands, Japan.

<span class="mw-page-title-main">PITX2</span> Protein-coding gene in the species Homo sapiens

Paired-like homeodomain transcription factor 2 also known as pituitary homeobox 2 is a protein that in humans is encoded by the PITX2 gene.

<span class="mw-page-title-main">KIF3A</span> Protein-coding gene in the species Homo sapiens

Kinesin-like protein KIF3A is a protein that in humans is encoded by the KIF3A gene.

<span class="mw-page-title-main">Nodal homolog</span> Mammalian protein found in Homo sapiens

Nodal homolog is a secretory protein that in humans is encoded by the NODAL gene which is located on chromosome 10q22.1. It belongs to the transforming growth factor beta superfamily. Like many other members of this superfamily it is involved in cell differentiation in early embryogenesis, playing a key role in signal transfer from the primitive node, in the anterior primitive streak, to lateral plate mesoderm (LPM).

Symmetry breaking in biology is the process by which uniformity is broken, or the number of points to view invariance are reduced, to generate a more structured and improbable state. Symmetry breaking is the event where symmetry along a particular axis is lost to establish a polarity. Polarity is a measure for a biological system to distinguish poles along an axis. This measure is important because it is the first step to building complexity. For example, during organismal development, one of the first steps for the embryo is to distinguish its dorsal-ventral axis. The symmetry-breaking event that occurs here will determine which end of this axis will be the ventral side, and which end will be the dorsal side. Once this distinction is made, then all the structures that are located along this axis can develop at the proper location. As an example, during human development, the embryo needs to establish where is ‘back’ and where is ‘front’ before complex structures, such as the spine and lungs, can develop in the right location. This relationship between symmetry breaking and complexity was articulated by P.W. Anderson. He speculated that increasing levels of broken symmetry in many-body systems correlates with increasing complexity and functional specialization. In a biological perspective, the more complex an organism is, the higher number of symmetry-breaking events can be found.

The Nodal signaling pathway is a signal transduction pathway important in regional and cellular differentiation during embryonic development.

In evolutionary developmental biology, inversion refers to the hypothesis that during the course of animal evolution, the structures along the dorsoventral (DV) axis have taken on an orientation opposite that of the ancestral form.

<span class="mw-page-title-main">Chirality</span> Difference in shape from a mirror image

Chirality is a property of asymmetry important in several branches of science. The word chirality is derived from the Greek χειρ (kheir), "hand", a familiar chiral object.

<span class="mw-page-title-main">Pareidae</span> Family of snakes

Pareidae is a small family of snakes found largely in southeast Asia, with an isolated subfamily endemic to southwestern India. It encompasses 42 species in four genera divided into two subfamilies: Pareinae and Xylophiinae. Both families are thought to have diverged from one another during the early-mid Eocene, about 40-50 million years ago.

<span class="mw-page-title-main">Axial Twist theory</span> Scientific theory in vertebrate development

The Axial Twist hypothesis is a scientific theory to explain a range of unusual aspects of the body plan of vertebrate animals. It proposes that the end-part of the head is turned around with respect to the rest of the body. This end-part consists of the face as well as part of the brain.

References

  1. 1 2 Little, RB; Norris, DP (February 2021). "Right, left and cilia: How asymmetry is established". Seminars in Cell & Developmental Biology. 110: 11–18. doi:10.1016/j.semcdb.2020.06.003. PMID   32571625. S2CID   219984175.
  2. ↑ Blum, M; Ott, T (2 April 2018). "Animal left-right asymmetry". Current Biology. 28 (7): R301–R304. doi: 10.1016/j.cub.2018.02.073 . PMID   29614284. S2CID   4613375.
  3. ↑ Hamada, H; Tam, P (2020). "Diversity of left-right symmetry breaking strategy in animals". F1000Research. 9: 123. doi: 10.12688/f1000research.21670.1 . PMC   7043131 . PMID   32148774.
  4. ↑ Blum, M; Feistel, K; Thumberger, T; Schweickert, A (April 2014). "The evolution and conservation of left-right patterning mechanisms". Development. 141 (8): 1603–13. doi: 10.1242/dev.100560 . PMID   24715452. S2CID   871667.
  5. ↑ Hamada, H; Tam, PP (2014). "Mechanisms of left-right asymmetry and patterning: driver, mediator and responder". F1000Prime Reports. 6: 110. doi: 10.12703/P6-110 . PMC   4275019 . PMID   25580264.
  6. ↑ Dasgupta, Agnik; Amack, Jeffrey D. (19 December 2016). "Cilia in vertebrate left–right patterning". Philosophical Transactions of the Royal Society B: Biological Sciences. 371 (1710): 20150410. doi:10.1098/rstb.2015.0410. PMC   5104509 . PMID   27821522.
  7. ↑ Gros, Jerome; Feistel, Kerstin; Viebahn, Christoph; Blum, Martin; Tabin, Clifford J. (15 May 2009). "Cell Movements at Hensen's Node Establish Left/Right Asymmetric Gene Expression in the Chick". Science. 324 (5929): 941–944. Bibcode:2009Sci...324..941G. doi:10.1126/science.1172478. PMC   2993078 . PMID   19359542.
  8. ↑ Hamada, Hiroshi; Tam, Patrick (19 February 2020). "Diversity of left-right symmetry breaking strategy in animals". F1000Research. 9: 123. doi: 10.12688/f1000research.21670.1 . PMC   7043131 . PMID   32148774.
  9. 1 2 Shimeld, Sebastian M.; Levin, Michael (2006-06-01). "Evidence for the regulation of left-right asymmetry in Ciona intestinalis by ion flux". Developmental Dynamics. 235 (6): 1543–1553. doi: 10.1002/dvdy.20792 . ISSN   1097-0177. PMID   16586445.
  10. 1 2 Molina, M Dolores; de Crozé, Noémie; Haillot, Emmanuel; Lepage, Thierry (2013-08-01). "Nodal: master and commander of the dorsal–ventral and left–right axes in the sea urchin embryo". Current Opinion in Genetics & Development. Developmental mechanisms, patterning and evolution. 23 (4): 445–453. doi:10.1016/j.gde.2013.04.010. PMID   23769944.
  11. ↑ Nishide, Kazuhiko; Mugitani, Michio; Kumano, Gaku; Nishida, Hiroki (2012-04-15). "Neurula rotation determines left-right asymmetry in ascidian tadpole larvae". Development. 139 (8): 1467–1475. doi: 10.1242/dev.076083 . ISSN   0950-1991. PMID   22399684.
  12. 1 2 Coutelis, J. B., González‐Morales, N., Géminard, C., & Noselli, S. (2014). Diversity and convergence in the mechanisms establishing L/R asymmetry in metazoa. EMBO Reports, e201438972.
  13. ↑ Spéder, Pauline; Ádám, Géza; Noselli, Stéphane (2006-04-06). "Type ID unconventional myosin controls left–right asymmetry in Drosophila". Nature. 440 (7085): 803–807. Bibcode:2006Natur.440..803S. doi:10.1038/nature04623. ISSN   0028-0836. PMID   16598259. S2CID   4412156.
  14. 1 2 3 Martín-Durán, José M.; Vellutini, Bruno C.; Hejnol, Andreas (2016-12-19). "Embryonic chirality and the evolution of spiralian left–right asymmetries". Phil. Trans. R. Soc. B. 371 (1710): 20150411. doi:10.1098/rstb.2015.0411. ISSN   0962-8436. PMC   5104510 . PMID   27821523.
  15. ↑ Asami, Takahiro; Cowie, Robert H.; Ohbayashi, Kako (1998-01-01). "Evolution of Mirror Images by Sexually Asymmetric Mating Behavior in Hermaphroditic Snails". The American Naturalist. 152 (2): 225–236. doi:10.1086/286163. JSTOR   10.1086/286163. PMID   18811387. S2CID   35119643.
  16. 1 2 Meshcheryakov, V. N.; Beloussov, L. V. (1975). "Asymmetrical rotations of blastomeres in early cleavage of gastropoda". Wilhelm Roux's Archives of Developmental Biology. 177 (3): 193–203. doi:10.1007/BF00848080. ISSN   0340-0794. PMID   28304794. S2CID   12448973.
  17. 1 2 Shibazaki, Yuichiro; Shimizu, Miho; Kuroda, Reiko (2004-08-24). "Body Handedness Is Directed by Genetically Determined Cytoskeletal Dynamics in the Early Embryo". Current Biology. 14 (16): 1462–1467. doi: 10.1016/j.cub.2004.08.018 . PMID   15324662.
  18. 1 2 Freeman, Gary; Lundelius, Judith W. (1982). "The developmental genetics of dextrality and sinistrality in the gastropodLymnaea peregra". Wilhelm Roux's Archives of Developmental Biology. 191 (2): 69–83. doi:10.1007/BF00848443. ISSN   0340-0794. PMID   28305091. S2CID   547508.
  19. ↑ Grande, Cristina; Patel, Nipam H. (2009-02-19). "Nodal signalling is involved in left–right asymmetry in snails". Nature. 457 (7232): 1007–1011. Bibcode:2009Natur.457.1007G. doi:10.1038/nature07603. ISSN   0028-0836. PMC   2661027 . PMID   19098895.
  20. 1 2 Shimizu, Keisuke; Iijima, Minoru; Setiamarga, Davin HE; Sarashina, Isao; Kudoh, Tetsuhiro; Asami, Takahiro; Gittenberger, Edi; Endo, Kazuyoshi (2013-01-01). "Left-right asymmetric expression of dpp in the mantle of gastropods correlates with asymmetric shell coiling". EvoDevo. 4 (1): 15. doi: 10.1186/2041-9139-4-15 . ISSN   2041-9139. PMC   3680195 . PMID   23711320.
  21. ↑ Kurita, Yoshihisa; Wada, Hiroshi (2011-04-27). "Evidence that gastropod torsion is driven by asymmetric cell proliferation activated by TGF-β signalling". Biology Letters. 7 (5): 759–762. doi:10.1098/rsbl.2011.0263. ISSN   1744-9561. PMC   3169068 . PMID   21525052.
  22. 1 2 3 Davison, Angus; McDowell, Gary S.; Holden, Jennifer M.; Johnson, Harriet F.; Koutsovoulos, Georgios D.; Liu, M. Maureen; Hulpiau, Paco; Roy, Frans Van; Wade, Christopher M. (2016). "Formin Is Associated with Left-Right Asymmetry in the Pond Snail and the Frog". Current Biology. 26 (5): 654–660. doi:10.1016/j.cub.2015.12.071. PMC   4791482 . PMID   26923788.
  23. 1 2 Kuroda, Reiko; Fujikura, Kohei; Abe, Masanori; Hosoiri, Yuji; Asakawa, Shuichi; Shimizu, Miho; Umeda, Shin; Ichikawa, Futaba; Takahashi, Hiromi (2016-10-06). "Diaphanous gene mutation affects spiral cleavage and chirality in snails". Scientific Reports. 6: 34809. Bibcode:2016NatSR...634809K. doi:10.1038/srep34809. ISSN   2045-2322. PMC   5052593 . PMID   27708420.
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