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Embryonic patterning in vertebrates is dependent upon the balance of inductive signals and their specific antagonists. We show that Noggin,  which encodes a bone morphogenetic protein (BMP) antagonist expressed in the node, notochord, and dorsal somite, is required for normal mouse development. Although  Noggin  has been implicated in neural induction, examination of null mutants in the mouse indicates that  Noggin  is not essential for this process. However, Noggin is required for subsequent growth and patterning of the neural tube. Early BMP-dependent dorsal cell fates, the roof plate and neural crest, form in the absence of Noggin. However, there is a progressive loss of early,  Sonic hedgehog ( Shh )-dependent ventral cell fates despite the normal expression of  Shh  in the notochord. Further, somite differentiation is deficient in both muscle and sclerotomal precursors. Addition of BMP2 or BMP4 to paraxial mesoderm explants blocks Shh-mediated induction of  Pax-1,  a sclerotomal marker, whereas addition of Noggin is sufficient to induce  Pax-1.  Noggin and Shh induce  Pax-1  synergistically. Use of protein kinase A stimulators blocks Shh-mediated induction of  Pax-1,  but not induction by Noggin, suggesting that induction is mediated by different pathways. Together these data demonstrate that inhibition of BMP signaling by axially secreted Noggin is an important requirement for normal patterning of the vertebrate neural tube and somite.

Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite