The vertebrate body plan is established during gastrulation, when cell
s move inwards to form the mesodermal and endodermal germ layers. Sign
als from a region of dorsal mesoderm, which is termed the organizer, p
attern the body axis by specifying the fates of neighbouring cells(1,2
). The organizer is itself induced by earlier signals(1). Although mem
bers of the transforming growth factor-beta (TGF-beta) and Wnt familie
s have been implicated in the formation of the organizer, no endogenou
s signalling molecule is known to be required for this process(1). Her
e we report that the zebrafish squint (sqt)(3) and cyclops (cyc)(4) ge
nes have essential, although partly redundant, functions in organizer
development and also in the formation of mesoderm and endoderm. We sho
w that the sqt gene encodes a member of the TGF-beta superfamily that
is related to mouse nodal. cyc encodes another nodal-related protein(5
,6), which is consistent with our genetic evidence that sqt and cyc ha
ve overlapping functions. The sqt gene is expressed in a dorsal region
of the blastula that includes the extraembryonic yolk syncytial layer
(YSL). The YSL has been implicated as a source of signals that induce
organizer development and mesendoderm formation(2,7). Misexpression o
f sqt RNA within the embryo or specifically in the YSL induces expande
d or ectopic dorsal mesoderm, These results establish an essential rol
e for nodal-related signals in organizer development and mesendoderm f
ormation.