Induction of the zebrafish ventral brain and floorplate requires cyclops/nodal signalling

Abstract

Zebrafish cyclops (cyc) mutations cause deficiencies in the dorsal mesendoderm¹,² and ventral neural tube³,⁴, leading to neural defects and cyclopia⁵,⁶. Here we report that cyc encodes a transforming growth factor-β (TGF-β)-related intercellular signalling molecule that is similar to mouse nodal⁷. cyc is expressed in dorsal mesendoderm at gastrulation and in the prechordal plate until early somitogenesis. Expression reappears transiently in the left lateral-plate mesoderm, and in an unprecedented asymmetric pattern in the left forebrain. Injection of cyc RNA non-autonomously restores sonic hedgehog -expressing cells of the ventral brain and floorplate that are absent in cyc mutants, whereas inducing activities are abolished by cyc^m294, a mutation of a conserved cysteine in the mature ligand. Our results indicate that cyc provides an essential non-cell-autonomous signal at gastrulation, leading to induction of the floorplate and ventral brain.