BMP signaling and skeletogenesis

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor (TGF)-β superfamily of signal molecules that mediate many diverse biological processes ranging from early embryonic tissue patterning to postnatal tissue homeostasis. BMPs trigger cell responses mainly through the canonical signaling pathway where intracellular Smads play central roles in delivering the extracellular signals to the nucleus. While the same Smads are used by BMPs in all types of cells, different transcription factors account in part for the functional diversity of BMPs. These transcription factors are recruited by Smads to regulate the expression of specific subsets of target genes depending on the cell types. Among the transcription factors are Hox proteins. Experimental gain and loss-of-function studies as well as naturally occurring mutations in Hox genes demonstrate their central roles in embryonic skeletal patterning. In addition to the interactions with Smads observed for several Hox proteins, there is also evidence that the expression of a number of Hox genes is regulated by BMPs. It is suggested that Hox proteins play an important role in the BMP pathway.