Regulation and Functional Analysis of Type X Collagen

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Bone morphogenetic proteins (BMP) are members of the transforming growth factor-b (TGF-b) family of cytokines that play a variety of different roles during animal development. Although BMPs were first identified for their bone-inducing abilities, surprisingly there is currently no in vivo evidence for a general requirement for BMP signaling in skeleton formation. Standard mouse knockouts for genes encoding BMP signaling proteins have not been very informative because many die during early embryogenesis before skeleton formation. We have performed conditional genetic studies and provide evidence that BMP type I receptors are essential and act redundantly for skeleton formation, thus revealing BMP signaling complexity. In combination with transgenic mice that express cre recombinase in limb mesenchyme and chondrocytes, we propose to examine the requirement and complexity of BMP signaling proteins in skeletal development.