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PMID:16712836

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Citation

Stottmann, RW, Berrong, M, Matta, K, Choi, M and Klingensmith, J (2006) The BMP antagonist Noggin promotes cranial and spinal neurulation by distinct mechanisms. Dev. Biol. 295:647-63

Abstract

Here we characterize the consequences of elevated bone morphogenetic protein (BMP) signaling on neural tube morphogenesis by analyzing mice lacking the BMP antagonist, Noggin. Noggin is expressed dorsally in the closing neural folds and ventrally in the notochord and somites. All Noggin-/- pups are born with lumbar spina bifida; depending on genetic background, they may also have exencephaly. The exencephaly is due to a primary failure of neurulation, resulting from a lack of mid/hindbrain dorsolateral hinge point (DLHP) formation. Thus, as previously shown for Shh signaling at spinal levels, BMP activity may inhibit cranial DLHP morphogenesis. However, the increased BMP signaling observed in the Noggin-/- dorsal neural tube is not sufficient to cause exencephaly; it appears to also depend on the action of a genetic modifier, which may act to increase dorsal Shh signaling. The spinal neural tube defect results from a different mechanism: increased BMP signaling in the mesoderm between the limb buds leads to abnormal somite differentiation and axial skeletal malformation. The resulting lack of mechanical support for the neural tube causes spina bifida. We show that this defect is due to elevated BMP4 signaling. Thus, Noggin is required for mammalian neurulation in two contexts, dependent on position along the rostrocaudal axis.

Links

PubMed PMC3001110 Online version:10.1016/j.ydbio.2006.03.051

Keywords

Animals; Bone Morphogenetic Protein 4; Bone Morphogenetic Proteins/antagonists & inhibitors; Carrier Proteins/physiology; Central Nervous System/embryology; Central Nervous System/growth & development; Embryonic Development; Embryonic Induction; Gene Expression Regulation, Developmental; Mice; Morphogenesis; Neural Tube Defects/etiology; Skull/embryology; Skull/innervation; Spine/embryology; Spine/innervation

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:BMP4

acts_upstream_of_or_within

GO:0048706: embryonic skeletal system development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2158495

P

  • results_in_development_of:(EMAPA:17674)

Seeded From UniProt

complete

MOUSE:BMP4

acts_upstream_of_or_within

GO:0048704: embryonic skeletal system morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2158495

P

Seeded From UniProt

complete

MOUSE:NOGG

acts_upstream_of_or_within

GO:0030514: negative regulation of BMP signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1862000

P

Seeded From UniProt

complete

MOUSE:NOGG

acts_upstream_of_or_within

GO:0021510: spinal cord development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1862000

P

Seeded From UniProt

complete

MOUSE:NOGG

acts_upstream_of_or_within

GO:0001843: neural tube closure

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1856173
MGI:MGI:1862000

P

Seeded From UniProt

complete

MOUSE:NOGG

acts_upstream_of_or_within

GO:0001839: neural plate morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1862000

P

Seeded From UniProt

complete

MOUSE:NOGG

acts_upstream_of_or_within

GO:2001234: negative regulation of apoptotic signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1862000

P

Seeded From UniProt

complete

MOUSE:NOGG

acts_upstream_of_or_within

GO:0061053: somite development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1862000

P

Seeded From UniProt

complete

MOUSE:NOGG

acts_upstream_of_or_within

GO:0060425: lung morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1862000

P

Seeded From UniProt

complete

MOUSE:NOGG

acts_upstream_of_or_within

GO:0048318: axial mesoderm development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1862000

P

  • results_in_development_of:(EMAPA:17214)

Seeded From UniProt

complete

MOUSE:NOGG

acts_upstream_of_or_within

GO:0060325: face morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1862000

P

Seeded From UniProt

complete

MOUSE:BMP4

acts_upstream_of_or_within

GO:0048704: embryonic skeletal system morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2158495

P

has_participant:(EMAPA:17674)

Seeded From UniProt

complete

MOUSE:BMP4

acts_upstream_of_or_within

GO:0048706: embryonic skeletal system development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2158495

P

results_in_development_of:(EMAPA:17674)

Seeded From UniProt

complete


See also

References

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