Bone morphogenetic proteins: an unconventional approach to isolation of first mammalian morphogens.

It is conventional to identify morphogens from fly and frog embryos during morphogenesis using gene-screens, subtractive hybridizations, differential displays and expression cloning. This information is then extended to mice and men. The bone morphogenetic proteins (BMPs) are a family of pleiotropic morphogens/cytokines isolated and cloned from the demineralized extracellular matrix of adult bone. Thus, BMPs were isolated from mammalian bone by an unconventional approach. BMPs initiate the sequential developmental cascade of bone morphogenesis in ectopic sites. The pleiotropic effects of BMPs on chemotaxis, mitosis and differentiation are based on concentration-dependent thresholds. Recent work has demonstrated the critical role of BMPs in pattern formation in amphibian and chick limb development. Targeted disruption of gene function by homologous recombination has demonstrated the actions of BMPs beyond bone in such disparate tissues as kidney, eye, testis, teeth, skin and heart. The successful isolation of first mammalian morphogens has laid the foundation for the elucidation of molecular signalling during morphogenesis in bones and beyond.