Regulation by members of the transforming growth factor beta superfamily of the digital and interdigital fates of the autopodial limb mesoderm

Embryonic limb outgrowth is accomplished by the proliferation of mesodermal cells in the progress zone. In this region, mesodermal cells are maintaine d in an undifferentiated and proliferating state by the action of the apica l ectodermal ridge (AER). Differentiation of these cells into individual sk eletal elements occurs when the cells are displaced proximally and leave th e influence of the AER as a consequence of the accumulation of cells in tha t region. Here we review the evidence obtained in the last few years showin g that members of the transforming growth factor beta (TGF beta) subfamily and bone morphogenetic proteins (BMPs) act as proximal signals in the autop od regulating the fate of the progress zone cells towards chondrogenesis or apoptosis. Our findings show that apoptosis is regulated by BMPs while cho ndrogenesis requires the interaction of TGF beta s and BMPs. Fibroblast gro wth factors (FGFs) produced by the AER exert an opposite function to both T GF beta s and BMPs, maintaining the progress zone cells in an undifferentia ted state.