Nodal Signaling: A Paradigm for TGFβ Signaling in Embryonic Development

Nodal signaling molecules are TGFβ family ligands that arose early during bilaterian evolution and are crucial for several key steps in embryonic development. They regulate the specification of mesoderm and endoderm, body patterning, left-right asymmetry, and pluripotency maintenance. Many of Nodal's effects are tissue specific and achieved through interaction with other signaling pathways. Nodal has become a paradigm for a morphogen that employs multiple mechanisms for tissue patterning, including concentration- and duration-dependent effects, feedback regulation, reaction-diffusion interactions, and scale invariance. Nodal signaling activates a broad set of target genes that specify cell types, remodel the intracellular and extracellular milieu, and drive cell movements and morphogenesis. While Nodal's developmental functions are largely conserved across vertebrates, many facets of the mechanisms that elicit transcriptional responses and pattern embryonic tissues remain to be clarified.