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???
The morphogenetic field concept was proposed by experimental embryologists to account for the self-regulative behavior of embryos. Such fields have remained an abstract concept until the recent identification of their molecular components using a combination of genetics, biochemistry, and theoretical modeling. One of the best studied models of a morphogenetic field is the Dorsal-Ventral (D-V) patterning of the early frog embryo. This patterning system is regulated by the bone morphogenetic protein (BMP) signaling pathway and an intricate network of secreted protein antagonists. This biochemical pathway of interacting proteins functions in the extracellular space to generate a D-V gradient of BMP signaling, which is maintained during extensive morphogenetic movements of cell layers during gastrulation. The D-V field is divided into a dorsal and a ventral center, in regions of low and high BMP signaling respectively, under opposite transcriptional control by BMPs. The robustness of the patterning is assured at two different levels. First, in the extracellular space by secreted BMP antagonists that generate a directional flow of BMP ligands to the ventral side. The flow is driven by the regulated proteolysis of the Chordin inhibitor and by the presence of a molecular sink on the ventral side that concentrates BMP signals. The tolloid metalloproteinases and the Chordin-binding protein Crossveinless-2 (CV2) are key components of this ventral sink. Second, by transcriptional feedback at the cellular level: The dorsal and ventral signaling centers adjust their size and level of BMP signaling by transcriptional feedback. This allows cells on one side of a gastrula containing about 10,000 cells to communicate with cells in the opposite pole of the embryo.
Ambrosio,
Crossveinless-2 Is a BMP feedback inhibitor that binds Chordin/BMP to regulate Xenopus embryonic patterning.
2008, Pubmed,
Xenbase
Ambrosio,
Crossveinless-2 Is a BMP feedback inhibitor that binds Chordin/BMP to regulate Xenopus embryonic patterning.
2008,
Pubmed
,
Xenbase
Ashe,
Local inhibition and long-range enhancement of Dpp signal transduction by Sog.
1999,
Pubmed
,
Xenbase
Bachiller,
The organizer factors Chordin and Noggin are required for mouse forebrain development.
2000,
Pubmed
Bachiller,
The role of chordin/Bmp signals in mammalian pharyngeal development and DiGeorge syndrome.
2003,
Pubmed
Ball,
Forging patterns and making waves from biology to geology: a commentary on Turing (1952) 'The chemical basis of morphogenesis'.
2015,
Pubmed
Ben-Zvi,
Scaling of the BMP activation gradient in Xenopus embryos.
2008,
Pubmed
,
Xenbase
Binnerts,
Human Crossveinless-2 is a novel inhibitor of bone morphogenetic proteins.
2004,
Pubmed
Chang,
Twisted gastrulation can function as a BMP antagonist.
2001,
Pubmed
,
Xenbase
Coffinier,
Mouse Crossveinless-2 is the vertebrate homolog of a Drosophila extracellular regulator of BMP signaling.
2002,
Pubmed
Collavin,
The secreted Frizzled-related protein Sizzled functions as a negative feedback regulator of extreme ventral mesoderm.
2003,
Pubmed
,
Xenbase
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
Crick,
Diffusion in embryogenesis.
1970,
Pubmed
Dale,
Xolloid-related: a novel BMP1/Tolloid-related metalloprotease is expressed during early Xenopus development.
2002,
Pubmed
,
Xenbase
De Robertis,
Evo-devo: variations on ancestral themes.
2008,
Pubmed
De Robertis,
Spemann's organizer and self-regulation in amphibian embryos.
2006,
Pubmed
De Robertis,
A common plan for dorsoventral patterning in Bilateria.
1996,
Pubmed
,
Xenbase
De Robertis,
Dorsal-ventral patterning and neural induction in Xenopus embryos.
2004,
Pubmed
,
Xenbase
De Robertis,
Gradient fields and homeobox genes.
1991,
Pubmed
Dorfman,
Biphasic activation of the BMP pathway patterns the Drosophila embryonic dorsal region.
2001,
Pubmed
Driever,
The bicoid protein determines position in the Drosophila embryo in a concentration-dependent manner.
1988,
Pubmed
Dyson,
The interpretation of position in a morphogen gradient as revealed by occupancy of activin receptors.
1998,
Pubmed
,
Xenbase
Eivers,
Integrating positional information at the level of Smad1/5/8.
2008,
Pubmed
,
Xenbase
Eldar,
Robustness of the BMP morphogen gradient in Drosophila embryonic patterning.
2002,
Pubmed
Faure,
Endogenous patterns of TGFbeta superfamily signaling during early Xenopus development.
2000,
Pubmed
,
Xenbase
Ferguson,
Localized enhancement and repression of the activity of the TGF-beta family member, decapentaplegic, is necessary for dorsal-ventral pattern formation in the Drosophila embryo.
1992,
Pubmed
Francois,
Dorsal-ventral patterning of the Drosophila embryo depends on a putative negative growth factor encoded by the short gastrulation gene.
1994,
Pubmed
Fuentealba,
Integrating patterning signals: Wnt/GSK3 regulates the duration of the BMP/Smad1 signal.
2007,
Pubmed
,
Xenbase
Garcia Abreu,
Chordin-like CR domains and the regulation of evolutionarily conserved extracellular signaling systems.
2002,
Pubmed
Gierer,
A theory of biological pattern formation.
1972,
Pubmed
Gregor,
Stability and nuclear dynamics of the bicoid morphogen gradient.
2007,
Pubmed
Groppe,
Structural basis of BMP signalling inhibition by the cystine knot protein Noggin.
2002,
Pubmed
Gurdon,
Direct and continuous assessment by cells of their position in a morphogen gradient.
1995,
Pubmed
Heemskerk,
Drosophila hedgehog acts as a morphogen in cellular patterning.
1994,
Pubmed
Holley,
A conserved system for dorsal-ventral patterning in insects and vertebrates involving sog and chordin.
1995,
Pubmed
,
Xenbase
Holley,
The Xenopus dorsalizing factor noggin ventralizes Drosophila embryos by preventing DPP from activating its receptor.
1996,
Pubmed
,
Xenbase
Ibañes,
Theoretical and experimental approaches to understand morphogen gradients.
2008,
Pubmed
Ikeya,
Essential pro-Bmp roles of crossveinless 2 in mouse organogenesis.
2006,
Pubmed
Inomata,
Robust stability of the embryonic axial pattern requires a secreted scaffold for chordin degradation.
2008,
Pubmed
,
Xenbase
Kamimura,
Vertebrate crossveinless 2 is secreted and acts as an extracellular modulator of the BMP signaling cascade.
2004,
Pubmed
Kicheva,
The Decapentaplegic morphogen gradient: a precise definition.
2008,
Pubmed
Kondo,
Bone morphogenetic proteins in the early development of zebrafish.
2007,
Pubmed
,
Xenbase
Lander,
Morpheus unbound: reimagining the morphogen gradient.
2007,
Pubmed
Larraín,
Proteolytic cleavage of Chordin as a switch for the dual activities of Twisted gastrulation in BMP signaling.
2001,
Pubmed
,
Xenbase
Lee,
Embryonic dorsal-ventral signaling: secreted frizzled-related proteins as inhibitors of tolloid proteinases.
2006,
Pubmed
,
Xenbase
Little,
Twisted gastrulation promotes BMP signaling in zebrafish dorsal-ventral axial patterning.
2004,
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
Martyn,
The ventralized ogon mutant phenotype is caused by a mutation in the zebrafish homologue of Sizzled, a secreted Frizzled-related protein.
2003,
Pubmed
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
McDowell,
Activin has direct long-range signalling activity and can form a concentration gradient by diffusion.
1997,
Pubmed
,
Xenbase
Mizutani,
Formation of the BMP activity gradient in the Drosophila embryo.
2005,
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,
Synexpression groups in eukaryotes.
1999,
Pubmed
,
Xenbase
Nunes da Fonseca,
Self-regulatory circuits in dorsoventral axis formation of the short-germ beetle Tribolium castaneum.
2008,
Pubmed
Oda,
Differing strategies for forming the arthropod body plan: lessons from Dpp, Sog and Delta in the fly Drosophila and spider Achaearanea.
2008,
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
Onichtchouk,
Silencing of TGF-beta signalling by the pseudoreceptor BAMBI.
1999,
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,
Dorsoventral patterning in Xenopus: inhibition of ventral signals by direct binding of chordin to BMP-4.
1996,
Pubmed
,
Xenbase
Plouhinec,
Systems biology of embryonic morphogens.
2007,
Pubmed
,
Xenbase
Reeves,
Quantitative models of developmental pattern formation.
2006,
Pubmed
Rentzsch,
Crossveinless 2 is an essential positive feedback regulator of Bmp signaling during zebrafish gastrulation.
2006,
Pubmed
Reversade,
Regulation of ADMP and BMP2/4/7 at opposite embryonic poles generates a self-regulating morphogenetic field.
2005,
Pubmed
,
Xenbase
Rogulja,
Regulation of cell proliferation by a morphogen gradient.
2005,
Pubmed
Ross,
Twisted gastrulation is a conserved extracellular BMP antagonist.
2001,
Pubmed
,
Xenbase
Rusch,
Threshold responses to the dorsal regulatory gradient and the subdivision of primary tissue territories in the Drosophila embryo.
1996,
Pubmed
Sakuragi,
Functional analysis of chick ONT1 reveals distinguishable activities among olfactomedin-related signaling factors.
2006,
Pubmed
,
Xenbase
Salic,
Sizzled: a secreted Xwnt8 antagonist expressed in the ventral marginal zone of Xenopus embryos.
1997,
Pubmed
,
Xenbase
Sasai,
Xenopus chordin: a novel dorsalizing factor activated by organizer-specific homeobox genes.
1994,
Pubmed
,
Xenbase
Schier,
Molecular genetics of axis formation in zebrafish.
2005,
Pubmed
Schmid,
Equivalent genetic roles for bmp7/snailhouse and bmp2b/swirl in dorsoventral pattern formation.
2000,
Pubmed
Schmierer,
TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility.
2007,
Pubmed
Schohl,
Beta-catenin, MAPK and Smad signaling during early Xenopus development.
2002,
Pubmed
,
Xenbase
Schulte-Merker,
The zebrafish organizer requires chordino.
1997,
Pubmed
,
Xenbase
Scott,
Homologues of Twisted gastrulation are extracellular cofactors in antagonism of BMP signalling.
2001,
Pubmed
,
Xenbase
Serpe,
The BMP-binding protein Crossveinless 2 is a short-range, concentration-dependent, biphasic modulator of BMP signaling in Drosophila.
2008,
Pubmed
Shimell,
The Drosophila dorsal-ventral patterning gene tolloid is related to human bone morphogenetic protein 1.
1991,
Pubmed
Shimmi,
Facilitated transport of a Dpp/Scw heterodimer by Sog/Tsg leads to robust patterning of the Drosophila blastoderm embryo.
2005,
Pubmed
Shimmi,
Physical properties of Tld, Sog, Tsg and Dpp protein interactions are predicted to help create a sharp boundary in Bmp signals during dorsoventral patterning of the Drosophila embryo.
2003,
Pubmed
Smith,
Expression cloning of noggin, a new dorsalizing factor localized to the Spemann organizer in Xenopus embryos.
1992,
Pubmed
,
Xenbase
Srinivasan,
Creation of a Sog morphogen gradient in the Drosophila embryo.
2002,
Pubmed
Sutherland,
Stepwise formation of a SMAD activity gradient during dorsal-ventral patterning of the Drosophila embryo.
2003,
Pubmed
Tucker,
The BMP signaling gradient patterns dorsoventral tissues in a temporally progressive manner along the anteroposterior axis.
2008,
Pubmed
Umulis,
Robust, bistable patterning of the dorsal surface of the Drosophila embryo.
2006,
Pubmed
von der Hardt,
The Bmp gradient of the zebrafish gastrula guides migrating lateral cells by regulating cell-cell adhesion.
2007,
Pubmed
Wang,
Spatial bistability of Dpp-receptor interactions during Drosophila dorsal-ventral patterning.
2005,
Pubmed
Wang,
Type IV collagens regulate BMP signalling in Drosophila.
2008,
Pubmed
Wolpert,
Positional information and the spatial pattern of cellular differentiation.
1969,
Pubmed
Wozney,
Novel regulators of bone formation: molecular clones and activities.
1988,
Pubmed
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
Zakin,
Development of the vertebral morphogenetic field in the mouse: interactions between Crossveinless-2 and Twisted Gastrulation.
2008,
Pubmed
,
Xenbase
Zeng,
Elucidation of subfamily segregation and intramolecular coevolution of the olfactomedin-like proteins by comprehensive phylogenetic analysis and gene expression pattern assessment.
2005,
Pubmed
Zhang,
Computational analysis of BMP gradients in dorsal-ventral patterning of the zebrafish embryo.
2007,
Pubmed
Zhang,
Crystal structure analysis reveals how the Chordin family member crossveinless 2 blocks BMP-2 receptor binding.
2008,
Pubmed
Zhang,
von Willebrand factor type C domain-containing proteins regulate bone morphogenetic protein signaling through different recognition mechanisms.
2007,
Pubmed
Zimmerman,
The Spemann organizer signal noggin binds and inactivates bone morphogenetic protein 4.
1996,
Pubmed
,
Xenbase
