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Nodal is considered a secretory protein that remains encoded by the gene “NODAL” in humans. It is located on chromosome 10q22.1 and belongs to the TGF-β or transforming growth factor beta superfamily.

Similar to other members that belong to this superfamily, nodal is included in cell differentiation in the early embryogenesis and so, it plays a vital role in signaling transfer from the note to LPM or lateral plate mesoderm.

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The Importance of Nodal Signaling

Nodal signaling is considered hugely vital in the development of endoderm and mesoderm formation besides subsequent organization of right-left axial structures. 


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Again, nodal has some important functions in stem cell maintenance, neural patterning, and many other processes of development that include right or left-handedness.

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A Few Species-Specific Ligands of Nodal

Nodal is a highly distributed cytokine and its presence isn’t confined to vertebrates only. This is also conserved in many deuterostomes, like tunicates, echinoderms, and cephalochordates as well as protostomes, like snails though neither the fruit fly Drosophila nor the nematode C. elegans possesses a copy of nodal.

Though human and mouse have got only one nodal gene, a zebrafish comprises 3 nodal paralogs, like southpaw, Cyclops, and squint. Again, the frogs have five. Though the zebrafish Nodal homologs tend to be hugely similar, there are some specialized parts for performing different roles. For example, Cyclops and Squint are vital for the formation of mesendoderm. On the other hand, the Southpaw performs a significant role in visceral left-right asymmetry and asymmetric heart morphogenesis.

You can take another instance of protein speciation of a frog where Xnr2 and Xnr1 regulate some movements in gastrulation contrary to Xnr6 and Xnr5 that are included in mesoderm induction. In mice, Nodal is implicated in left-right asymmetry, mesoderm induction, and neural patterning.

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What are the Functions of Nodal Signaling?

Nodal signaling is responsible for regulating the formation of mesoderm in some species-specific manner. And so, in Xenopus, Xnr does control dorsoventral mesoderm formation besides the marginal zone. In zebrafish, Cyclops and squint remain liable for animal-vegetal formation of mesoderm. But in mouse and chicken, Nodal and Vg1 endorse the formation of the primitive streaks in the epiblast. In the development of chicks, Nodal gets expressed in Koller’s sickle. According to studies it has been discovered that a nodal knockout in a mouse remains responsible for the absence of a primitive streak.


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Endoderm specification needs an advanced expression of Nodal in comparison to mesoderm specification. In this instance, Nodal does stimulate mixer homeoproteins and they have an interaction with SMADs for upregulating endoderm-specific genes.

Recent research done on hESCs or human embryonic stem cells and mouse signify that Nodal is included in the preservation of pluripotent potentials and stem cell self-renewal.

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