Bone morphogenetic protein signaling in limb outgrowth and patterning.

Bone morphogenetic proteins (BMPs) are multifunctional growth factors belonging to the transforming growth factor beta (TGFbeta) multigene family. Current evidence indicates that they may play different and even antagonistic roles at different stages of limb development. Refined studies of their function in these processes have been impeded in the mouse due to the early lethality of null mutants for several BMP ligands and their receptors. Recently, however, these questions have benefited from the very powerful Cre-loxP technology. In this review, I intend to summarize what has been learned from this conditional mutagenesis approach in the mouse limb, focusing on Bmp2, Bmp4 and Bmp7 while restricting my analysis to the initial phases of limb formation and patterning. Two major aspects are discussed, the role of BMPs in dorsal-ventral polarization of the limb bud, together with their relation to apical ectodermal ridge (AER) induction, and their role in controlling digit number and identity. Particular attention is paid to the methodology, its power and its limits.