Nodal signaling in vertebrate development.
TGFss signals belonging to the Nodal family set up the embryonic axes, induce mesoderm and endoderm, pattern the nervous system, and determine left-right asymmetry in vertebrates. Nodal signaling activates a canonical TGFss pathway involving activin receptors, Smad2 transcription factors, and FoxH1 coactivators. In addition, Nodal signaling is dependent on coreceptors of the EGF-CFC family and antagonized by the Lefty and Cerberus families of secreted factors. Additional modulators of Nodal signaling include convertases that regulate the generation of the mature signal, and factors such as Arkadia and DRAP1 that regulate the cellular responses to the signal. Complex regulatory cascades and autoregulatory loops coordinate Nodal signaling during early development. Nodals have concentration-dependent roles and can act both locally and at a distance. These studies demonstrate that Nodal signaling is modulated at almost every level to precisely orchestrate tissue patterning during vertebrate embryogenesis.
Developmental Genetics Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA. schier@saturn.med.nyu.edu
Alexander F
AF
Schier
D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D004622:Embryo, Mammalian / Q000196:embryology* / Q000502:physiology; D004625:Embryo, Nonmammalian; D025461:Feedback, Physiological / Q000502:physiology; D007839:Functional Laterality / Q000502:physiology*; D006801:Humans; D055457:Nodal Protein; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014714:Vertebrates / Q000196:embryology* / Q000502:physiology
C526007:NODAL protein, human; D055457:Nodal Protein; D016212:Transforming Growth Factor beta