Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
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.
???displayArticle.pubmedLink???
19733655
???displayArticle.pmcLink???PMC2803698 ???displayArticle.link???Mech Dev ???displayArticle.grants???[+]
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.
Akiyama-Oda,
Axis specification in the spider embryo: dpp is required for radial-to-axial symmetry transformation and sog for ventral patterning.
2006, Pubmed
Akiyama-Oda,
Axis specification in the spider embryo: dpp is required for radial-to-axial symmetry transformation and sog for ventral patterning.
2006,
Pubmed
Ambrosio,
Crossveinless-2 Is a BMP feedback inhibitor that binds Chordin/BMP to regulate Xenopus embryonic patterning.
2008,
Pubmed
,
Xenbase
Bachiller,
The organizer factors Chordin and Noggin are required for mouse forebrain development.
2000,
Pubmed
Benito-Gutiérrez,
CNS evolution: new insight from the mud.
2009,
Pubmed
Ben-Zvi,
Scaling of the BMP activation gradient in Xenopus embryos.
2008,
Pubmed
,
Xenbase
Bouwmeester,
Cerberus is a head-inducing secreted factor expressed in the anterior endoderm of Spemann's organizer.
1996,
Pubmed
,
Xenbase
Carrasco,
Cloning of an X. laevis gene expressed during early embryogenesis coding for a peptide region homologous to Drosophila homeotic genes.
1984,
Pubmed
,
Xenbase
Cho,
Overexpression of a homeodomain protein confers axis-forming activity to uncommitted Xenopus embryonic cells.
1991,
Pubmed
,
Xenbase
Coffinier,
Mouse Crossveinless-2 is the vertebrate homolog of a Drosophila extracellular regulator of BMP signaling.
2002,
Pubmed
Conley,
Crossveinless 2 contains cysteine-rich domains and is required for high levels of BMP-like activity during the formation of the cross veins in Drosophila.
2000,
Pubmed
Dale,
Xolloid-related: a novel BMP1/Tolloid-related metalloprotease is expressed during early Xenopus development.
2002,
Pubmed
,
Xenbase
De Robertis,
Spemann's organizer and self-regulation in amphibian embryos.
2006,
Pubmed
De Robertis,
Dorsal-ventral patterning and neural induction in Xenopus embryos.
2004,
Pubmed
,
Xenbase
De Robertis,
Gradient fields and homeobox genes.
1991,
Pubmed
De Robertis,
The molecular ancestry of segmentation mechanisms.
2008,
Pubmed
De Robertis,
A common plan for dorsoventral patterning in Bilateria.
1996,
Pubmed
,
Xenbase
De Robertis,
Evo-devo: variations on ancestral themes.
2008,
Pubmed
Dirksen,
A novel, activin-inducible, blastopore lip-specific gene of Xenopus laevis contains a fork head DNA-binding domain.
1992,
Pubmed
,
Xenbase
Duboule,
The rise and fall of Hox gene clusters.
2007,
Pubmed
Eivers,
Mad is required for wingless signaling in wing development and segment patterning in Drosophila.
2009,
Pubmed
,
Xenbase
Francois,
Dorsal-ventral patterning of the Drosophila embryo depends on a putative negative growth factor encoded by the short gastrulation gene.
1994,
Pubmed
Glinka,
Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction.
1998,
Pubmed
,
Xenbase
Gont,
Tail formation as a continuation of gastrulation: the multiple cell populations of the Xenopus tailbud derive from the late blastopore lip.
1993,
Pubmed
,
Xenbase
Green,
Responses of embryonic Xenopus cells to activin and FGF are separated by multiple dose thresholds and correspond to distinct axes of the mesoderm.
1992,
Pubmed
,
Xenbase
Heasman,
Patterning the early Xenopus embryo.
2006,
Pubmed
,
Xenbase
Heasman,
Morpholino oligos: making sense of antisense?
2002,
Pubmed
,
Xenbase
Holley,
The Xenopus dorsalizing factor noggin ventralizes Drosophila embryos by preventing DPP from activating its receptor.
1996,
Pubmed
,
Xenbase
Holley,
A conserved system for dorsal-ventral patterning in insects and vertebrates involving sog and chordin.
1995,
Pubmed
,
Xenbase
Hurtado,
Neural induction in the absence of organizer in salamanders is mediated by MAPK.
2007,
Pubmed
,
Xenbase
Inomata,
Robust stability of the embryonic axial pattern requires a secreted scaffold for chordin degradation.
2008,
Pubmed
,
Xenbase
Jürgens,
Mutations affecting the pattern of the larval cuticle inDrosophila melanogaster : II. Zygotic loci on the third chromosome.
1984,
Pubmed
Kao,
Lithium-induced respecification of pattern in Xenopus laevis embryos.
,
Pubmed
,
Xenbase
Kelley,
A concentration-dependent endocytic trap and sink mechanism converts Bmper from an activator to an inhibitor of Bmp signaling.
2009,
Pubmed
Khokha,
Depletion of three BMP antagonists from Spemann's organizer leads to a catastrophic loss of dorsal structures.
2005,
Pubmed
,
Xenbase
Kuroda,
Default neural induction: neuralization of dissociated Xenopus cells is mediated by Ras/MAPK activation.
2005,
Pubmed
,
Xenbase
Lee,
Embryonic dorsal-ventral signaling: secreted frizzled-related proteins as inhibitors of tolloid proteinases.
2006,
Pubmed
,
Xenbase
Levi-Montalcini,
The nerve growth factor thirty-five years later.
1987,
Pubmed
Little,
Extracellular modulation of BMP activity in patterning the dorsoventral axis.
2006,
Pubmed
,
Xenbase
Lowe,
Dorsoventral patterning in hemichordates: insights into early chordate evolution.
2006,
Pubmed
Marqués,
Production of a DPP activity gradient in the early Drosophila embryo through the opposing actions of the SOG and TLD proteins.
1997,
Pubmed
,
Xenbase
Mason,
Dorsal midline fate in Drosophila embryos requires twisted gastrulation, a gene encoding a secreted protein related to human connective tissue growth factor.
1994,
Pubmed
Moos,
Anti-dorsalizing morphogenetic protein is a novel TGF-beta homolog expressed in the Spemann organizer.
1995,
Pubmed
,
Xenbase
Muraoka,
Sizzled controls dorso-ventral polarity by repressing cleavage of the Chordin protein.
2006,
Pubmed
Niehrs,
The homeobox gene goosecoid controls cell migration in Xenopus embryos.
1993,
Pubmed
,
Xenbase
Niehrs,
Synexpression groups in eukaryotes.
1999,
Pubmed
,
Xenbase
O'Connor,
Shaping BMP morphogen gradients in the Drosophila embryo and pupal wing.
2006,
Pubmed
Oelgeschläger,
Chordin is required for the Spemann organizer transplantation phenomenon in Xenopus embryos.
2003,
Pubmed
,
Xenbase
Oelgeschläger,
The evolutionarily conserved BMP-binding protein Twisted gastrulation promotes BMP signalling.
2000,
Pubmed
,
Xenbase
Pera,
Exploration of the extracellular space by a large-scale secretion screen in the early Xenopus embryo.
2005,
Pubmed
,
Xenbase
Pera,
Neural and head induction by insulin-like growth factor signals.
2001,
Pubmed
,
Xenbase
Pera,
A direct screen for secreted proteins in Xenopus embryos identifies distinct activities for the Wnt antagonists Crescent and Frzb-1.
2000,
Pubmed
,
Xenbase
Pera,
Integration of IGF, FGF, and anti-BMP signals via Smad1 phosphorylation in neural induction.
2003,
Pubmed
,
Xenbase
Piccolo,
Cleavage of Chordin by Xolloid metalloprotease suggests a role for proteolytic processing in the regulation of Spemann organizer activity.
1997,
Pubmed
,
Xenbase
Piccolo,
The head inducer Cerberus is a multifunctional antagonist of Nodal, BMP and Wnt signals.
1999,
Pubmed
,
Xenbase
Piccolo,
Dorsoventral patterning in Xenopus: inhibition of ventral signals by direct binding of chordin to BMP-4.
1996,
Pubmed
,
Xenbase
Plouhinec,
Systems biology of the self-regulating morphogenetic gradient of the Xenopus gastrula.
2009,
Pubmed
,
Xenbase
Pueyo,
Ancestral Notch-mediated segmentation revealed in the cockroach Periplaneta americana.
2008,
Pubmed
Ralston,
Long-range Dpp signaling is regulated to restrict BMP signaling to a crossvein competent zone.
2005,
Pubmed
Rentzsch,
Crossveinless 2 is an essential positive feedback regulator of Bmp signaling during zebrafish gastrulation.
2006,
Pubmed
Reversade,
Depletion of Bmp2, Bmp4, Bmp7 and Spemann organizer signals induces massive brain formation in Xenopus embryos.
2005,
Pubmed
,
Xenbase
Reversade,
Regulation of ADMP and BMP2/4/7 at opposite embryonic poles generates a self-regulating morphogenetic field.
2005,
Pubmed
,
Xenbase
Ronshaugen,
The Drosophila microRNA iab-4 causes a dominant homeotic transformation of halteres to wings.
2005,
Pubmed
Sander,
The opposing homeobox genes Goosecoid and Vent1/2 self-regulate Xenopus patterning.
2007,
Pubmed
,
Xenbase
Sasai,
Regulation of neural induction by the Chd and Bmp-4 antagonistic patterning signals in Xenopus.
1995,
Pubmed
,
Xenbase
Sasai,
Xenopus chordin: a novel dorsalizing factor activated by organizer-specific homeobox genes.
1994,
Pubmed
,
Xenbase
Serpe,
The BMP-binding protein Crossveinless 2 is a short-range, concentration-dependent, biphasic modulator of BMP signaling in Drosophila.
2008,
Pubmed
Smith,
Expression cloning of noggin, a new dorsalizing factor localized to the Spemann organizer in Xenopus embryos.
1992,
Pubmed
,
Xenbase
Spemann,
Induction of embryonic primordia by implantation of organizers from a different species. 1923.
2001,
Pubmed
Taira,
The LIM domain-containing homeo box gene Xlim-1 is expressed specifically in the organizer region of Xenopus gastrula embryos.
1992,
Pubmed
,
Xenbase
Wessely,
Analysis of Spemann organizer formation in Xenopus embryos by cDNA macroarrays.
2004,
Pubmed
,
Xenbase
Wessely,
xBtg-x regulates Wnt/beta-Catenin signaling during early Xenopus development.
2005,
Pubmed
,
Xenbase
Xie,
Twisted gastrulation enhances BMP signaling through chordin dependent and independent mechanisms.
2005,
Pubmed
Yabe,
Ogon/Secreted Frizzled functions as a negative feedback regulator of Bmp signaling.
2003,
Pubmed
,
Xenbase
Yekta,
MicroRNA-directed cleavage of HOXB8 mRNA.
2004,
Pubmed
Yu,
Axial patterning in cephalochordates and the evolution of the organizer.
2007,
Pubmed
Zakin,
Development of the vertebral morphogenetic field in the mouse: interactions between Crossveinless-2 and Twisted Gastrulation.
2008,
Pubmed
,
Xenbase
Zhang,
Crystal structure analysis reveals how the Chordin family member crossveinless 2 blocks BMP-2 receptor binding.
2008,
Pubmed
Zimmerman,
The Spemann organizer signal noggin binds and inactivates bone morphogenetic protein 4.
1996,
Pubmed
,
Xenbase
