Cooperation and regulatory loops of multiple nodals are essential for mesendoderm patterning in early embryos. Essential for mesoderm formation and axial patterning during embryonic development. Activates the activin-like signaling pathway to induce dorsal and ventral mesoderm in animal cap ectoderm. In addition, also dorsalizes ventral marginal zone (VMZ) tissues during gastrulation. Acts in a downstream signaling cascade via cripto and cer1 to mediate cardiogenesis in embryonic mesoderm. Directs the orientation of the left-right axis by driving the left-specific gene cascade in the left lateral plate mesoderm. Homodimer; disulfide-linked (By similarity). Interacts with, and is inhibited by cer1 and gdf10/bmp3b. In the first phase of expression, localized to the vegetal region of the blastula. During gastrulation (stage 10.5), this expression disappears and instead becomes localized to the dorsal marginal zone, with enrichment in the organizer. During the second phase of expression in neurulae and tailbud embryos, expression restarts firstly in two symmetric patches near the posterior end of the notochord, and then in a large asymmetrical domain in the left lateral plate mesoderm. Has two phases of temporal expression during embryogenesis; first expressed at late blastula (stage 9) with expression peaking at early gastrula. Expression then disappears before restarting in a second phase in late neurulae (stage 17). By dorsal mesoderm-inducing signals including smad2-smad4, activin and other nodal-related proteins including nodal2/nr-2 and nodal4/nr-4. Shows autoinduction by nodal/nr-1. Induced by vegt, acting in an autoregulatory loop. Beta-catenin potentiates the response to activin. Not induced by wnt8 alone, but wnt8 potentiates the response to activin. Suppressed by ventral inducers such as bmp4. Belongs to the TGF-beta family.