The Xenopus dorsalizing factor Gremlin identifies a novel family of secreted proteins that antagonize BMP activities.
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.
Hsu
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DR
Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
Economides
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AN
Wang
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Eimon
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PM
Harland
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RM
D028341:Activins; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D003001:Cloning, Molecular; D016207:Cytokines; D004625:Embryo, Nonmammalian / Q000737:chemistry; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental; D007265:Inhibins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009432:Neural Crest / Q000502:physiology; D055456:Nodal Signaling Ligands; D009865:Oocytes / Q000502:physiology; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D014981:Xenopus / Q000196:embryology*; D029867:Xenopus Proteins
C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016207:Cytokines; C486400:GREM1 protein, Xenopus; C490088:Grem2 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C490085:NBL1 protein, Xenopus; C113775:Ndr2 protein, vertebrate; D055456:Nodal Signaling Ligands; D011506:Proteins; C485173:STK38L protein, Xenopus; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; C100866:cer1 protein, Xenopus; D028341:Activins; D007265:Inhibins