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Genes & Development
Article . 1998 . Peer-reviewed
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Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite

Authors: Chen-Ming Fan; Lyle B. Zimmerman; Jill A. McMahon; Andrew P. McMahon; Shinji Takada; Richard M. Harland;

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

Abstract

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.

Keywords

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

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    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%
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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).
BIP!Citations provided by BIP!
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.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
763
Top 1%
Top 1%
Top 0.1%
Published in a Diamond OA journal