The zebrafish Nodal signal Squint functions as a morphogen

Secreted morphogens induce distinct cellular responses in a concentration-dependent manner and act directly at a distance(1-7). The existence of morphogens during mesoderm induction and patterning in vertebrates has been highly controversial, and it remains unknown whether endogenous mesoderm inducers act directly as morphogens(8-10), function locally(9) or act through relay mechanisms(11-12). Here we test the morphogen properties of Cyclops and Squint-two Nodal-related transforming growth factor-beta signals required for mesoderm formation and patterning in zebrafish(13-16). Whereas different levels of both Squint and Cyclops can induce different downstream genes(14,17-19), we rnd that only Squint can function directly at a distance. These results indicate that Squint acts as a secreted morphogen that does not require a relay mechanism.