Background：

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 Nod