Bone morphogenetic proteins: Multifunctional regulators of vertebrate development

A recurrent theme in embryonic development and tissue regeneration is that cells communicate with each other using just a handful of conserved families of signaling molecules. One of the largest of these multifunctional families is that of the bone morphogenetic proteins (BMPs), with >20 members identified in organisms ranging from sea urchin to mammals (Fig. II. The name BMP was first given to three proteins purified hom a demineralized bovine bone preparation that induced ectopic cartilage and endochondral bone when implanted in experimental animals (Wozney et al. 1988). One of these proteins (BMP1) was a putative protease of the astacin family, whereas the other two (BMP2 and BMP3) were related to human transforming growth factor beta (TGF beta). It is now clear that the name BMP is misleading because there is strong generic and experimental evidence that these molecules regulate biological processes as diverse as cell proliferation, apoptosis, differentiation, cell-fate determination, and morphogenesis. Moreover, the vertebrate BMPs are involved in the development of nearly all organs and tissues, including the nervous system, somites, lung, kidney, skin, and gonads, as well as in critical steps in the establishment of the basic embryonic body plan. This review focuses on recent studies related to BMP function in vertebrates, particularly those involving mutations of BMP-encoding genes in mice. Additional information about the larger TGF beta superfamily can be found in other reviews (Kingsley 1994a,b, McPherron and Lee 1996). The complexity of the numerous trans-membrane serine-threonine kinases that act as BMP signaling receptors precludes full discussion here, but again, a number of excellent reviews are available, in addition to those cited above (Massague et al. 1994, Massague and Weis-Garcia 1996).