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Embryos and developing organs have the remarkable ability of self-regenerating after experimental manipulations. In the Xenopus blastula half-embryos can regenerate the missing part, producing identical twins. Studies on the molecular nature of Spemann's organizer have revealed that self-regulation results from the battle between two signaling centers under reciprocal transcriptional control. Long-range communication between the dorsal and ventral sides is mediated by the action of growth factor antagonists - such as the BMP antagonist Chordin - that regulate the flow of BMPs within the embryonic morphogenetic field. BMPs secreted by the dorsal Spemann organizer tissue are released by metalloproteinases of the Tolloid family, which cleave Chordin at a distance of where they were produced. The dorsal center secretes Chordin, Noggin, BMP2 and ADMP. The ventral center of the embryo secretes BMP4, BMP7, Sizzled, Crossveinless-2 and Tolloid-related. Crossveinless-2 binds Chordin/BMP complexes, facilitating their flow towards the ventral side, where BMPs are released by Tolloid allowing peak BMP signaling. Self-regulation occurs because transcription of ventral genes is induced by BMP while transcription of dorsal genes is repressed by BMP signals. This assures that for each action of Spemann's organizer there is a reaction in the ventral side of the embryo. Because both dorsal and ventral centers express proteins of similar biochemical activities, they can compensate for each other. A novel biochemical pathway of extracellular growth factor signaling regulation has emerged from these studies in Xenopus. This remarkable dorsal-ventral positional information network has been conserved in evolution and is ancestral to all bilateral animals.
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Fig. 13. Simultaneous depletion of four BMPs causes ubiquitousCNS differentiation, which can be restored by transplantation of either a wild-type ventral center or a dorsal organizer. (A) Control Xenopus embryo showing normal Sox2 mRNA expression in the CNS. (B) Sibling depleted of ADMP, BMP2, 4 and 7 with antisense morpholinos; note that the entire embryonic surface is covered by CNStissue. (C) Transplantation of a wild-type ventral center (labeled with nuclear LacZ lineage tracer) into BMP-depleted embryos restores formation of a neural plate with epidermis ventrally to it. (D) Cytokeratin mRNA is abundantly expressed in epidermis. (E) Cytokeratin expression is eliminated in BMP-depleted embryos (because epidermis is replaced by CNS). (F) Transplantation of a wild-type dorsal organizer rescues BMP depletion. Epidermis is induced, but at a considerable distance from the transplanted tissue (which gives rise to notochord). BMP does not signal close to the graft because it is inhibited by Chordin. These experiments show, first, that BMP inhibition causes ubiquitous neural induction and, second, that the embryo has dorsal and ventral sources of BMP signals. Experiments from Reversade and De Robertis (2005), reproduced with permission.
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