BMP-3 is a novel inhibitor of both activin and BMP-4 signaling in Xenopus embryos.
In Xenopus, the biological effects of BMP-3 oppose those of ventralizing BMPs, but the mechanism for this antagonism remains unclear. Here, we demonstrate that BMP-3 is a dorso-anteriorizing factor in Xenopus embryos that interferes with both activin and BMP signaling. BMP-3 acts by binding to ActRIIB, the common type II receptor for these proteins. Once BMP-3 binds to ActRIIB, it cannot be competed off by excess ligand making a receptor complex that is unable to activate R-Smads and transduce signal. Consistent with a model where BMP-3 interferes with activin and BMPs through a shared receptor, we show that overexpression of BMP-3 can only be rescued by co-injection of xActRIIB. Our results identify BMP-3 as a novel antagonist of both activin and BMPs and uncover how some of the diverse developmental processes that are regulated by both activin and BMP signaling can be modulated during embryogenesis.
Gamer
Laura W
LW
Department of Oral and Developmental Biology, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA. laura_gamer@hsdm.harvard.edu
Nove
John
J
Levin
Michael
M
Rosen
Vicki
V
D030301:Activin Receptors, Type II / Q000235:genetics / Q000378:metabolism; D028341:Activins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D055398:Bone Morphogenetic Protein 3; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental; D008954:Models, Biological; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D014981:Xenopus / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins
D055398:Bone Morphogenetic Protein 3; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D012333:RNA, Messenger; D029867:Xenopus Proteins; C525812:bmp4 protein, Xenopus; D028341:Activins; D030301:Activin Receptors, Type II; C425584:activin receptor type II-B