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Publication : Gremlin is the BMP antagonist required for maintenance of Shh and Fgf signals during limb patterning.

First Author  Khokha MK Year  2003
Journal  Nat Genet Volume  34
Issue  3 Pages  303-7
PubMed ID  12808456 Mgi Jnum  J:84077
Mgi Id  MGI:2665160 Doi  10.1038/ng1178
Citation  Khokha MK, et al. (2003) Gremlin is the BMP antagonist required for maintenance of Shh and Fgf signals during limb patterning. Nat Genet 34(3):303-7
abstractText  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.
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