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Abstract
Using a Xenopus expression-cloning screen, we have isolated Gremlin, a novel antagonist
of bone morphogenetic protein (BMP) signaling that is expressed in the neural crest.
Gremlin belongs to a novel gene family that includes the head-inducing factor Cerberus
and the tumor suppressor DAN. We show that all family members are secreted proteins
and that they act as BMP antagonists in embryonic explants. We also provide support
for the model that Gremlin, Cerberus, and DAN block BMP signaling by binding BMPs,
preventing them from interacting with their receptors. In addition, Cerberus alone
blocks signaling by Activin- and Nodal-like members of the TGF beta superfamily. Therefore,
we propose that Gremlin, Cerberus, and DAN control diverse processes in growth and
development by selectively antagonizing the activities of different subsets of the
TGF beta ligands.