title: Regulation of ADMP and BMP2/4/7 at opposite embryonic poles generates a self-regulating morphogenetic field.
abstract: Embryos have the ability to self-regulate and regenerate normal structures after being sectioned in half. How is such a morphogenetic field established? We discovered that quadruple knockdown of ADMP and BMP2/4/7 in Xenopus embryos eliminates self-regulation, causing ubiquitous neural induction throughout the ectoderm. ADMP transcription in the Spemann organizer is activated at low BMP levels. When ventral BMP2/4/7 signals are depleted, Admp expression increases, allowing for self-regulation. ADMP has BMP-like activity and signals via the ALK-2 receptor. It is unable to signal dorsally because of inhibition by Chordin. The ventral BMP antagonists Sizzled and Bambi further refine the pattern. By transplanting dorsal or ventral wild-type grafts into ADMP/BMP2/4/7-depleted hosts, we demonstrate that both poles serve as signaling centers that can induce histotypic differentiation over considerable distances. We conclude that dorsal and ventral BMP signals and their extracellular antagonists expressed under opposing transcriptional regulation provide a molecular mechanism for embryonic self-regulation.
authors.affiliation: Howard Hughes Medical Institute and Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Bruno
authors.initials: B
authors.lastname: Reversade
authors.forename: E M
authors.initials: EM
authors.lastname: De Robertis
mesh_terms: D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000187:drug effects / Q000502:physiology*; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000235:genetics / Q000502:physiology*; D002352:Carrier Proteins / Q000008:administration & dosage / Q000235:genetics; D002490:Central Nervous System / Q000196:embryology / Q000378:metabolism; D038681:Follistatin / Q000235:genetics; D006023:Glycoproteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D008666:Metalloendopeptidases / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D008845:Microinjections; D009154:Mutation; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics; D020897:Organizers, Embryonic / Q000378:metabolism / Q000502:physiology / Q000637:transplantation; D010766:Phosphorylation / Q000187:drug effects; D011506:Proteins / Q000235:genetics; D051898:Smad1 Protein / Q000378:metabolism; D016378:Tissue Transplantation; D055394:Tolloid-Like Metalloproteinases; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000502:physiology; D000099176:Noggin Protein
chemical_list: D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D052005:Bone Morphogenetic Protein Receptors, Type I; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D038681:Follistatin; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008666:Metalloendopeptidases; D020319:Oligodeoxyribonucleotides, Antisense; D011506:Proteins; D051898:Smad1 Protein; D055394:Tolloid-Like Metalloproteinases; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; D000099176:Noggin Protein; C504610:Bmp2 protein, Xenopus; C499481:MADH1 protein, Xenopus; C477670:TWSG1 protein, Xenopus; C499591:admp protein, Xenopus; C121859:bambi-A protein, Xenopus; C525812:bmp4 protein, Xenopus; C525822:bmp7.1 protein, Xenopus; C100866:cer1 protein, Xenopus; C109976:szl protein, Xenopus; C054234:chordin; C575919:tll1 protein, Xenopus