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Embryonic patterning in vertebrates is dependent upon the balance of inductive signals and their specific antagonists. We show thatNoggin, 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.
Central Nervous System, Colforsin, Bone Morphogenetic Protein 2, Gene Expression Regulation, Developmental, Mice, Inbred Strains, Bone Morphogenetic Protein 4, Cyclic AMP-Dependent Protein Kinases, Hindlimb, DNA-Binding Proteins, Mesoderm, Mice, Inbred C57BL, Embryonic and Fetal Development, Mice, 1-Methyl-3-isobutylxanthine, Bone Morphogenetic Proteins, Cyclic AMP, Animals, Hedgehog Proteins, Carrier Proteins, In Situ Hybridization
Central Nervous System, Colforsin, Bone Morphogenetic Protein 2, Gene Expression Regulation, Developmental, Mice, Inbred Strains, Bone Morphogenetic Protein 4, Cyclic AMP-Dependent Protein Kinases, Hindlimb, DNA-Binding Proteins, Mesoderm, Mice, Inbred C57BL, Embryonic and Fetal Development, Mice, 1-Methyl-3-isobutylxanthine, Bone Morphogenetic Proteins, Cyclic AMP, Animals, Hedgehog Proteins, Carrier Proteins, In Situ Hybridization
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | 763 | |
popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network. | Top 1% | |
influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | Top 1% | |
impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network. | Top 0.1% |