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

TY - JOUR

T1 - Gremlin is the BMP antagonist required for maintenance of Shh and Fgf signals during limb patterning

AU - Khokha, M K

AU - Hsu, D

AU - Brunet, L J

AU - Dionne, M S

AU - Harland, R M

PY - 2003/7/1

Y1 - 2003/7/1

N2 - 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

AB - 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

U2 - 10.1038/ng1178

DO - 10.1038/ng1178

M3 - Article

SN - 1546-1718

VL - 34

SP - 303

EP - 307

JO - Nature Genetics

JF - Nature Genetics

IS - 3

ER -