Cell-cell communication is mediated by secreted proteins such as Notch, Hedgehog, Wingless, Fibroblast Growth Factor (FGF), Epidermal Growth Factor (EFG) and Transforming Growth Factor-beta (TGF-beta) and their respective cell surface receptors. The TGF-beta superfamily includes TGF-beta, Activin, Nodal, Mullerian inhibiting substance (MIS), growth and differentiation factor (GDF) and bone morphogenetic proteins (BMPs). BMPs have been implicated in limb growth and patterning. The joints are formed after initial cartilage condensation followed by cell death and cavitation. The BMPs function by binding to a receptor complex that is found on all normal cells and is composed of type-I and –II receptors. BMP activities are modulated through gene expression, protein processing and by interaction with antagonists. The interplay between BMPs and their antagonists governs developmental and cellular processes as diverse as establishment of the embryonic dorsal-ventral axis, induction of neuronal tissue, formation of joints in the skeletal system and the neurogenesis in the adult brain. The BMP anagonists include the Differential screening-selected gene Aberrant in Neuroblastoma (DAN) family members (DAN, Cerberus, Gremlin), Chordin, Noggin and SOG. Noggin inhibits BMP signaling by blocking the molecular interfaces of the binding epitopes for both type-I and –II receptors. Noggin is a homodimer (~32kDa) of two monomeric units linked together by a disulfide bond. The monomeric precursor (232aa, human and mouse) is encoded by NOG gene, mapped at human chromosome 17. The mature protein (28-232aa) is secreted as a glycosylated dimer which binds to BMPs including BMP-2, -4 and–7. The structure of Noggin is very similar to BMP-7. Mutation in Noggin gene leads to skeletal dysplasias characterized by joint fusions.