GDF3, a BMP inhibitor, regulates cell fate in stem cells and early embryos

The TGFbeta superfamily of ligands plays key functions in development and disease. In both human and mouse embryonic stem cells, a member of this family, GDF3, is specifically expressed in the pluripotent state. We show that GDF3 is an inhibitor of its own subfamily, blocks classic BMP signaling in multiple contexts, interacts with BMP proteins and is expressed specifically in the node during gastrulation in a pattern consistent with BMP inhibition. Furthermore, we use gain- and reduction-of-function to show that in a species-specific manner, GDF3 regulates both of the two major characteristics of embryonic stem cells: the ability to maintain the undifferentiated state and the ability to differentiate into the full spectrum of cell types.