Bone morphogenetic proteins regulate interdigital cell death in the avian embryo.

The embryonic limb bud provides an excellent model for analyzing the mechanisms that regulate programmed cell death during development. At the time of digit formation in the developing autopod, the undifferentiated distal mesodermal cells may undergo or chondrogenic differentiation or apoptosis depending whether they are incorporated into the future digital rays or into the interdigital spaces. Both chondrogenesis or apoptosis are induced by local BMPS. However, whereas the chondrogenic-promoting activity of BMPs appears to be regulated through the BMPR-1b receptor, the mechanism by which the BMPs execute the death program remains unknown. The BMP proapoptotic activity requires the expression of members of the msx family of closely related homeobox-containing genes and is finally mediated by caspase activation, but the nature of the caspase(s) directly responsible for the cell death is also unknown. Finally, other growth factors present in the developing autopod at the stages of digit formation such as members of the FGF and TGF beta families modulate the ability of BMPs to induce cell death or chondrogenesis.