The zebrafish Nodal signal Squint functions as a morphogen

Abstract

Secreted morphogens induce distinct cellular responses in a concentration-dependent manner and act directly at a distance^{1,2,3,4,5,6,7}. 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^8,9,10, function locally⁹ or act through relay mechanisms^11,12. Here we test the morphogen properties of Cyclops and Squint—two Nodal-related transforming growth factor-β signals required for mesoderm formation and patterning in zebrafish^13,14,15,16. Whereas different levels of both Squint and Cyclops can induce different downstream genes^14,17,18,19, we find 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.