TGF-beta Superfamily Signaling Pathways Throughout Development

It is now possible to modify the mouse genome to generate transgenic mice with precise genetic mutations, and thousands of such models have now been created. For over a decade, our laboratory has been using knockout and knockin transgenic mouse studies to define TGF-beta superfamily signaling pathways and function. In our efforts to understand reproduction in vivo, we have produced transgenic knockout models for studying TGFb superfamily ligands (e.g., growth differentiation factor 9, bone morphogenetic protein 15, activins, and inhibins), a ligand binding protein (e.g., follistatin), a receptor (e.g., ACVR2), a putative downstream receptor binding protein (e.g., FKBP12), downstream SMADs (e.g., SMAD5), and a downstream target (e.g., pentraxin 3). These investigations have revealed that TGF-beta superfamily ligands, receptors, SMADs, and upstream and downstream regulators function in diverse developmental and physiological pathways. We are extending our studies by using new technology such as Cre-loxP strategies to address the in vivo roles of these and additional proteins in mammalian reproduction.