Genetic differentiation of the vertebrate somite necessitates a balance of inductive signals and antagonists. Noggin is a secreted protein that binds and inactivates members of the transforming growth factor-beta (TGFβ) superfamily of signaling proteins, such as bone morphogenetic proteins-2, 4, 7 (BMP2, BMP4, BMP7). Inhibition of BMP signaling by axially secreted Noggin mediates normal vertebrate skeletogenesis and patterning of the neural tube and somite. Spatially, Noggin may effectively antagonize BMP activity by efficiently diffusing through extracellular matrices, thereby creating morpho-genic gradients. Mice embryos that are homozygous null for Noggin, a lethal genotype, display stubby, continuous limbs with lack of joints in the paws and an array of other developmental defects.