The transforming growth factor-beta (TGF-beta) superfamily encompasses a la
rge group of structurally related polypeptides that are capable of regulati
ng cell growth and differentiation in a wide range of embryonic and adult t
issues(1). Growth/differentiation factor-1 (Gdf-1. encoded by Gdf1) is a TG
F-beta family member of unknown function that was originally isolated from
an early mouse embryo cDNA library(2) and is expressed specifically in the
nervous system in late-stage embryos and adult mice(3). Here we show that a
t early stages of mouse development, Gdf1 is expressed initially throughout
the embryo proper and then most prominently in the primitive node, ventral
neural tube, and intermediate and lateral plate mesoderm. To examine its b
iological function, we generated a mouse line carrying a targeted mutation
in Gdf1. Gdf1(-/-) mice exhibited a spectrum of defects related to left-rig
ht axis formation, including visceral situs inversus, right pulmonary isome
rism and a range of cardiac anomalies. In most Gdf1(-/-) embryos, the expre
ssion of Ebaf (formerly lefty-1) in the left side of the floor plate and Le
ftb (formerly lefty-2), nodal and Pitx2 in the left lateral plate mesoderm
was absent, suggesting that Gdf1 acts upstream of these genes either direct
ly or indirectly to activate their expression. Our findings suggest that Gd
f1 acts early in the pathway of gene activation that leads to the establish
ment of left-right asymmetry.