Recombinant Mouse Gremlin Protein

Gremlin was identified in a Xenopus expression-cloning screen as a dorsalizing factor that can induce a secondary axis. A rat homolog, called Drm, was identified as a cDNA that was downregulated in v-mos transfected cells. Gremlin/Drm belongs to the DAN family of secreted glycoproteins that are BMP antagonists. Other members of the family include: cerberus, Dante, PRDC, caronte and DAN. DAN family members share a cysteine-rich domain that is structurally related to the cysteine-knot motif found in TGF-beta superfamily ligands. In vitro, Gremlin/Drm binds BMP-4 and BMP-2 indicating that it might interfere with BMP signaling. Gremlin/Drm acts as a BMP-2/4 antagonist in a variety of tissues and developmental processes including: Xenopus animal cap explants, chick limb bud outgrowth and chondrogenesis, murine lung branching morphogenesis, and osteogenic differentiation of mouse myoblasts and bone marrow stromal cells. In addition, expression of Gremlin/Drm has been shown to be downregulated in a wide range of human cancer cell lines. Mouse, human, chick and Xenopus homologs of Gremlin share over 80% amino acid identity. It is likely that various DAN family members and other BMP antagonists including Noggin, Chordin, Follistatin and TSG can selectively antagonize the activities of different subsets of TGF-beta superfamily ligands.