Transforming growth factor beta and mouse development.

Transforming growth factor beta has many biological effects including the control of cellular growth, differentiation, migration and extracellular matrix production; these are all processes essential for normal development. Although mice first generated more than eight years ago, bearing mutations in TGF beta ligands demonstrated the importance of TGF beta-induced signal transduction pathways for development in mammals but complete functional analysis is still lacking. Here, the current state-of-the-art in mouse development is reviewed. As a basis for understanding function, the principle features of mouse development over the 21 days of pregnancy are described and illustrated, from fertilization of the egg to mid-gestation when organogenesis is largely complete. This is completed with a description of when and where TGF beta ligands, receptors and downstream signalling molecules are expressed as the mouse embryo develops. The functions of TGF beta in preimplantation development, in implantation of the embryos in the uterine wall and in postimplantation development are then described through a review of the literature on gene ablation of the ligands, receptors and downstream molecules, or the ectopic expression of dominant negative forms of the receptors in vivo, which interfere with normal signal transduction. The evidence confirms multifunctional roles at all stages of development.