Noggin (NOG) is an embryonic inducer that can sequester TGF-β cytokines of the BMP family with extremely high affinity. This protein was originally identified as a BMP-4 antagonist whose action is critical for proper formation of the head and other dorsal structures. NOG also has been shown to modulate the activities of other BMPs including BMP-2, -7, -13, and -14. It is expressed in defined areas of the adult central nervous system and peripheral tissues such as lung, skeletal muscle, and skin. During culture of human embryonic stem cells (hESC) or neural stem cells under certain conditions, addition of NOG to antagonize BMP activity may allow stem cells to proliferate while maintaining their undifferentiated state, or alternatively, to differentiate into dopaminergic neurons. NOG also appears to maintain adult stem cell populations in vivo. For example, it maintains neural stem cells within the hippocampus. Targeted deletion of NOG in mice results in prenatal death and recessive phenotype displaying a severely malformed skeletal system. Conversely, transgenic mice over-expressing NOG in mature osteoblasts display impaired osteoblastic differentiation, reduced bone formation, and severe osteoporosis.