How do embryos know their left side from right ? Role of Nodal signalling in Left-right asymmetry in Snails – PART II

By | May 7, 2021
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The mechanism involving in the complex process of LR symmetry ,especially in vertebrates is slowly getting more and more clear.The mechanism that leads to this asymmetry is predominantly dominated by signalling molecule Nodal, a member of the transforming growth factor-b superfamily, that – in all vertebrates checked to date – is expressed on the left side of the body and necessary to set up left-right asymmetry.In vertebrates, a set of genes tells the body it has to form a heart toward one side, and nodal is one of those genes and complete loss of nodal function produces a randomization of the left–right asymmetry of visceral organs.Orthologues of Nodal can be found in other deuterostomes like ascidians and sea urchins but Nodal is conspicuous by its absence in other two main clades of Bilateria: Ecdysozoa (includes flies and nematodes) and Lophotrochozoa (includes snails and annelids),suggesting there was no common strategy in the common ancestor of humans, snails and other bilateral organisms for generating left-right asymmetry.As a result, biologists have assumed that fruit flies and all other non-deuterostomes – snails included – use some other mechanism to establish right and left. Fruit flies and nematodes are in the clade Ecdysozoa, while snails and worms are members of the clade Lophotrochozoa.

Just to remind you the classification of animals: Bilateria can be divided into Protostomes ( includes ecdysozoa and Lophotrochozoa) and Deuterostomes can be classified into : Chordata, Echinodermata, Hemichordata and Xenoturbella.Chordata which includes Vertebrates ,Urochoradata,e.g. Ascidians, Cephalaochordata e.g.Amphioxus.)

Cristina Grande and Nipam patel reported the presence of gene “Nodal” and its downstream effector “Pitx” in the journal Nature ,which suggest that this cellular pathway was already present in ancestor of bmost animals and might have lost in Ecdysozoans like Drosophila and Nematodes, hence they evolved a different strategy for generating LR asymmetry.

According to Nipam patel,this finding of Nodal implication in LR in clade Lophotrochozoa could help to track down the ultimate cause of symmetry-breaking in snails and other organisms, and the cascade of gene activation that leads to complex shapes, such as coiled shells.

As described before that asymmetric expression and function of Nodal is a conserved feature of Deuterostomes and in protostomes so far Nodal pathway doesnot seems to be involved in assigning LR asymmetry during the embryonic development. To gain more insights into molecular mechanisms of LR asymmetry in lophotrochozoans, Grande and Patel focused on members of the Nodal pathway in two species of snails that differ in chirality: the sinistral species Biomphalaria glabrata, an intermediate host for the pathogen that causes schistosomiasis, and the dextral species Lottia gigantean.

Grande Isolated nodal and Pitx (one of the targets of Nodal signalling) in these two species of snails and found that the side of the embryo that expresses nodal and Pitx is related to body chirality: both genes are expressed on the right side of the embryo in the dextral (right-handed) species Lottia gigantea and on the left side in the sinistral (left-handed) species Biomphalaria glabrata.

To further confirm the data obtained by the expression of nodal and pitx in attaining LR asymmetry ,Grande performed pharmacological inhibition the Nodal pathway and found that nodal acts upstream of Pitx, and that some treated animals developed with a loss of shell chirality.

To know whether Nodal is present in other lophotrochozoans also or an unique feature of snails ,they looked into the genome sequence of annelid, Capitella. Grande fiound orthologues of both Nodal and pitx, suggesting that nodal is active throughout the Lophotrochozoa.

Before this discovery by Nipam patel and Christina Grande ,e verybody were of the notion that use of Nodal and pitx for attaining LR asymmetry was an invention of deuterostomes but now with the discovery of the presence and role (in snails) of Nodal and pitx in lophotrochozoans suggests that the ancestor of all bilaterians already used these genes to set up left-right asymmetry.

Because the ancestral snail was right-handed and thus, presumably, expressed nodal and Pitx on the right side of the body – similar to sea urchins, an early offshoot of the deuterostome branch leading to humans – the authors propose that the common ancestor of all bilateral animals had left-right asymmetry controlled by nodal and Pitx expressed on the right side of the body.The discovery also could help Grande and Patel track down the maternal factors that ultimately determine handedness in snails.

Journal reference:

Nodal signalling is involved in left-right asymmetry in snails.
Grande C, Patel NH.
Nature. 2008 Dec 21. PMID: 19098895