The Nodal signaling pathway is a signal transduction pathway important in regional and cellular differentiation during embryonic development.[1]

The Nodal family of proteins, a subset of the transforming growth factor beta (TGFβ) superfamily, is responsible for mesoendoderm induction, patterning of the nervous system, and determination of dorsal- ventral axis in vertebrate embryos. Activation of the Nodal pathway involves nodal binding to activin and activin-like receptors which leads to phosphorylation of the Smad2. The P-Smad2/Smad4 complex translocates into the nucleus to interact with transcription factors such as FoxH1, p53 and Mixer (Xenopus mix-like endodermal regulator). This will, in turn, lead to induction of target genes such as NODAL, Lefty, the antagonist of nodal cerberus, and others
The Lefty proteins, divergent members of the TGFβ superfamily of proteins, act as extracellular antagonists of Nodal signaling. Expression studies of the Lefty homologue, antivin, in zebrafish show that Lefty likely acts as a competitive inhibitor of Nodal signaling.
The receptor for activin represents a novel subclass of cell surface receptors with serine/threonine kinase activity. Activin binds both type I (50–55 kDa) and type II (70–75 kDa) receptors13, both of which are members of the receptor serine/threonine kinase family14, along with TGFβ and BMP. There are two type I receptors (ALK2 and ALK4)14 and at least three type II receptors, type II, type IIB and type IIA-N15. Type I and II receptors form a stable complex after ligand binding, with the type I receptor being phosphorylated through the kinase activity of the type II receptor