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PMID:12808456
| Citation |
Khokha, MK, Hsu, D, Brunet, LJ, Dionne, MS and Harland, RM (2003) Gremlin is the BMP antagonist required for maintenance of Shh and Fgf signals during limb patterning. Nat. Genet. 34:303-7 |
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| Abstract |
During limb outgrowth, signaling by bone morphogenetic proteins (BMPs) must be moderated to maintain the signaling loop between the zone of polarizing activity (ZPA) and the apical ectodermal ridge (AER). Gremlin, an extracellular Bmp antagonist, has been proposed to fulfill this function and therefore be important in limb patterning. We tested this model directly by mutating the mouse gene encoding gremlin (Cktsf1b1, herein called gremlin). In the mutant limb, the feedback loop between the ZPA and the AER is interrupted, resulting in abnormal skeletal pattern. We also show that the gremlin mutation is allelic to the limb deformity mutation (ld). Although Bmps and their antagonists have multiple roles in limb development, these experiments show that gremlin is the principal BMP antagonist required for early limb outgrowth and patterning. |
| Links |
PubMed Online version:10.1038/ng1178 |
| Keywords |
Animals; Body Patterning; Bone Morphogenetic Proteins/antagonists & inhibitors; Bone Morphogenetic Proteins/physiology; Bone and Bones/metabolism; Embryonic Induction; Female; Fetal Proteins/metabolism; Fibroblast Growth Factor 4; Fibroblast Growth Factors/genetics; Fibroblast Growth Factors/metabolism; Forelimb/embryology; Gene Expression Regulation, Developmental; Hedgehog Proteins; Hindlimb/embryology; Intercellular Signaling Peptides and Proteins; Limb Buds/cytology; Limb Buds/embryology; Loss of Heterozygosity; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microfilament Proteins; Mutation; Nuclear Proteins/metabolism; Proteins/physiology; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Signal Transduction; Trans-Activators/metabolism |
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Significance
Annotations
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