Regulation of ADMP and BMP2/4/7 at Opposite Embryonic Poles Generates a Self-Regulating Morphogenetic Field

• Published in: Cell 2005-12, Vol.123 (6), p.1147-1160
• Main Authors: Reversade, Bruno, De Robertis, E.M.
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Body Patterning - drug effects; Body Patterning - physiology; Bone Morphogenetic Protein 2; Bone Morphogenetic Protein 4; Bone Morphogenetic Protein 7; Bone Morphogenetic Protein Receptors, Type I - metabolism; Bone Morphogenetic Proteins - administration & dosage; Bone Morphogenetic Proteins - genetics; Bone Morphogenetic Proteins - physiology; Carrier Proteins - administration & dosage; Carrier Proteins - genetics; Central Nervous System - embryology; Central Nervous System - metabolism; Follistatin - genetics; Glycoproteins - administration & dosage; Glycoproteins - genetics; Glycoproteins - metabolism; Intercellular Signaling Peptides and Proteins - administration & dosage; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - metabolism; Intracellular Signaling Peptides and Proteins - metabolism; Membrane Proteins - genetics; Membrane Proteins - physiology; Metalloendopeptidases - administration & dosage; Metalloendopeptidases - genetics; Metalloendopeptidases - metabolism; Microinjections; Mutation; Oligodeoxyribonucleotides, Antisense - genetics; Organizers, Embryonic - metabolism; Organizers, Embryonic - physiology; Organizers, Embryonic - transplantation; Phosphorylation - drug effects; Proteins - genetics; Smad1 Protein - metabolism; Tissue Transplantation; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - physiology; Xenopus; Xenopus laevis - embryology; Xenopus laevis - genetics; Xenopus laevis - physiology; Xenopus Proteins - genetics; Xenopus Proteins - metabolism; Xenopus Proteins - physiology
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2005.08.047

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.