Functions
Nodal signaling regulates mesoderm formation in a species-specific manner. Thus, in Xenopus, Xnr controls dorso-ventral mesoderm formation along the marginal zone. In zebrafish, Squint and Cyclops are responsible for animal-vegetal mesoderm formation. In chicken and mouse, Vg1 and Nodal respectively promote primitive streak formation in the epiblast. Studies have shown that a nodal knockout in mouse causes the absence of the primitive streak and failure in the formation of mesoderm, leading to developmental arrest just after gastrulation.
Compared to mesoderm specification, endoderm specification requires a higher expression of Nodal. Here, Nodal stimulates mixer homeoproteins, which can interact with SMADs in order to up-regulate endoderm specific genes and repress mesoderm specific genes.
Left-right (LR) asymmetry of visceral organs in vertebrates is also established through nodal signaling. Whereas Nodal is initially symmetrically expressed in the embryo, after gastrulation, Nodal becomes asymmetrically restricted to the left side of the organism. It is highly conserved among deuterostomes. An ortholog of Nodal was recently found in snails and was shown to be involved in left-right asymmetry as well.
In order to enable anterior neural tissue development, Nodal signaling needs to be repressed after inducing mesendoderm and LR symmetry.
Recent research on mouse and human embryonic stem cells (hESCs) indicates that Nodal seems to be involved in the maintenance of stem cell self-renewal and pluripotent potentials. Thus, overexpression of Nodal in hESCs lead to the repression of cell differentiation. On the contrary, inhibition of Nodal and Activin signaling enabled the differentiation of hESCs.
Read more about this topic: NODAL
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—Ralph Waldo Emerson (1803–1882)
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—Edward T. Hall (b. 1914)