Growth and Differentiation Factor 1 (GDF 1) is a secreted protein in the TGF beta superfamily (1). It is the functional equivalent of frog, zebrafish, and chick Vg1 (2, 3). Human GDF 1 is synthesized as a preproprotein that produces an approximately 44 kDa proprotein after cleavage of a 29 amino acid (aa) signal peptide. Further proteolysis at a dibasic cleavage site produces a 224 aa propeptide and a secreted 119 aa, 12 15 kDa mature peptide (4). Mature human GDF 1 shares 81% aa sequence identity with mouse and rat GDF 1. GDF 1 is expressed in the developing and adult nervous system, particularly in neurons of the cerebral cortex and hippocampus (4, 5). It is required during embryogenesis for development of left/right axis asymmetry, anterior/posterior axis asymmetry, and the notochord (2, 3, 6, 7). It cooperates with Nodal and GDF 3 in these activities and potentiates Nodal bioactivity through formation of a 27 kDa noncovalent GDF 1 Nodal heterodimer (3, 7, 8). The presence of Nodal is required for GDF 1 i