Nodal signaling and the zebrafish organizer

Systematic genetic screens in zebrafish have led to the discovery of mutati ons that affect organizer function and development. The molecular isolation and phenotypic analysis of the affected genes have revealed that TGF-beta signals of the Nodal family play a key role in organizer formation. The act ivity of the Nodal signals Cyclops and Squint is regulated extracellularly by the EGF-CFC cofactor One-eyed Pinhead and by antagonists belonging to th e Lefty family of TGF-beta molecules. In the absence of Nodal signaling, th e fate of cells in the organizer is transformed from dorsal mesoderm to neu ral ectoderm. Differential Nodal signaling also patterns the organizer alon g the anterior-posterior axis, with high levels required for anterior cell fates and lower levels for posterior fates. In addition, Nodal signaling co operates with the homeodomain transcription factor Bozozok in organizer for mation and neural patterning. The combination of genetic, molecular and emb ryological approaches in zebrafish has thus provided a framework to underst and the mechanisms underlying organizer development.