INDUCTION OF THE ZEBRAFISH VENTRAL BRAIN AND FLOORPLATE REQUIRES CYCLOPS NODAL SIGNALING/

Zebrafish cyclops (cyc) mutations cause deficiencies in the dorsal mes endoderm(1,2) and ventral neural tube(3,4), leading to neural defects and cyclopia(5,6). Here we report that cyc encodes a transforming grow th factor-beta (TGF-beta)-related intercellular signalling molecule th at is similar to mouse nodal(7). cyc is expressed in dorsal mesendoder m at gastrulation and in the prechordal plate until early somitogenesi s. Expression reappears transiently in the left lateral-plate mesoderm , and in an unprecedented asymmetric pattern in the left forebrain. In jection of cyc RNA non-autonomously restores sonic hedgehog-expressing cells of the ventral brain and floorplate that are absent in cyc muta nts, whereas inducing activities are abolished by cyc(m294), a mutatio n of a conserved cysteine in the mature ligand. Our results indicate t hat cyc provides an essential non-cell-autonomous signal at gastrulati on, leading to induction of the floorplate and ventral brain.