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???
We review the current status of research in dorsal-ventral (D-V) patterning in vertebrates. Emphasis is placed on recent work on Xenopus, which provides a paradigm for vertebrate development based on a rich heritage of experimental embryology. D-V patterning starts much earlier than previously thought, under the influence of a dorsal nuclear -Catenin signal. At mid-blastula two signaling centers are present on the dorsal side: The prospective neuroectoderm expresses bone morphogenetic protein (BMP) antagonists, and the future dorsal endoderm secretes Nodal-related mesoderm-inducing factors. When dorsal mesoderm is formed at gastrula, a cocktail of growth factor antagonists is secreted by the Spemann organizer and further patterns the embryo. A ventralgastrula signaling center opposes the actions of the dorsal organizer, and another set of secreted antagonists is produced ventrally under the control of BMP4. The early dorsal -Catenin signal inhibits BMP expression at the transcriptional level and promotes expression of secreted BMP antagonists in the prospective central nervous system (CNS). In the absence of mesoderm, expression of Chordin and Noggin in ectoderm is required for anteriorCNS formation. FGF (fibroblast growth factor) and IGF (insulin-like growth factor) signals are also potent neural inducers. Neural induction by anti-BMPs such as Chordin requires mitogen-activated protein kinase (MAPK) activation mediated by FGF and IGF. These multiple signals can be integrated at the level of Smad1. Phosphorylation by BMP receptor stimulates Smad1 transcriptional activity, whereas phosphorylation by MAPK has the opposite effect. Neural tissue is formed only at very low levels of activity of BMP-transducing Smads, which require the combination of both low BMP levels and high MAPK signals. Many of the molecular players that regulate D-V patterning via regulation of BMP signaling have been conserved between Drosophila and the vertebrates.
Agathon,
The molecular nature of the zebrafish tail organizer.
2003, Pubmed
Agathon,
The molecular nature of the zebrafish tail organizer.
2003,
Pubmed Agius,
Endodermal Nodal-related signals and mesoderm induction in Xenopus.
2000,
Pubmed
,
Xenbase Arendt,
Comparison of early nerve cord development in insects and vertebrates.
1999,
Pubmed Aubert,
Functional gene screening in embryonic stem cells implicates Wnt antagonism in neural differentiation.
2002,
Pubmed Aubin,
In vivo convergence of BMP and MAPK signaling pathways: impact of differential Smad1 phosphorylation on development and homeostasis.
2004,
Pubmed Avsian-Kretchmer,
Comparative genomic analysis of the eight-membered ring cystine knot-containing bone morphogenetic protein antagonists.
2004,
Pubmed 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 Baker,
Wnt signaling in Xenopus embryos inhibits bmp4 expression and activates neural development.
1999,
Pubmed
,
Xenbase Beddington,
Axis development and early asymmetry in mammals.
1999,
Pubmed Bertocchini,
The hypoblast of the chick embryo positions the primitive streak by antagonizing nodal signaling.
2002,
Pubmed
,
Xenbase Binnerts,
Human Crossveinless-2 is a novel inhibitor of bone morphogenetic proteins.
2004,
Pubmed Blitz,
Twisted gastrulation loss-of-function analyses support its role as a BMP inhibitor during early Xenopus embryogenesis.
2003,
Pubmed
,
Xenbase Bouwmeester,
Cerberus is a head-inducing secreted factor expressed in the anterior endoderm of Spemann's organizer.
1996,
Pubmed
,
Xenbase Bradley,
Different activities of the frizzled-related proteins frzb2 and sizzled2 during Xenopus anteroposterior patterning.
2000,
Pubmed
,
Xenbase Chang,
Twisted gastrulation can function as a BMP antagonist.
2001,
Pubmed
,
Xenbase Cho,
Molecular nature of Spemann's organizer: the role of the Xenopus homeobox gene goosecoid.
1991,
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 Connors,
The role of tolloid/mini fin in dorsoventral pattern formation of the zebrafish embryo.
1999,
Pubmed Dale,
Xolloid-related: a novel BMP1/Tolloid-related metalloprotease is expressed during early Xenopus development.
2002,
Pubmed
,
Xenbase del Barco Barrantes,
Dkk1 and noggin cooperate in mammalian head induction.
2003,
Pubmed
,
Xenbase De Robertis,
The establishment of Spemann's organizer and patterning of the vertebrate embryo.
2000,
Pubmed
,
Xenbase De Robertis,
A common plan for dorsoventral patterning in Bilateria.
1996,
Pubmed
,
Xenbase Eldar,
Robustness of the BMP morphogen gradient in Drosophila embryonic patterning.
2002,
Pubmed Fainsod,
On the function of BMP-4 in patterning the marginal zone of the Xenopus embryo.
1994,
Pubmed
,
Xenbase Garcia Abreu,
Chordin-like CR domains and the regulation of evolutionarily conserved extracellular signaling systems.
2002,
Pubmed Gawantka,
Antagonizing the Spemann organizer: role of the homeobox gene Xvent-1.
1995,
Pubmed
,
Xenbase Glinka,
Head induction by simultaneous repression of Bmp and Wnt signalling in Xenopus.
1997,
Pubmed
,
Xenbase Glinka,
Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction.
1998,
Pubmed
,
Xenbase Goerttler,
[Not Available].
1925,
Pubmed Gonzalez,
Head and trunk in zebrafish arise via coinhibition of BMP signaling by bozozok and chordino.
2000,
Pubmed Groppe,
Structural basis of BMP signalling inhibition by the cystine knot protein Noggin.
2002,
Pubmed Hammerschmidt,
Dorsoventral patterning in the zebrafish: bone morphogenetic proteins and beyond.
2002,
Pubmed
,
Xenbase Hansen,
Direct neural induction and selective inhibition of mesoderm and epidermis inducers by Xnr3.
1997,
Pubmed
,
Xenbase Haramoto,
Xenopus tropicalis nodal-related gene 3 regulates BMP signaling: an essential role for the pro-region.
2004,
Pubmed
,
Xenbase Hardcastle,
FGF-8 stimulates neuronal differentiation through FGFR-4a and interferes with mesoderm induction in Xenopus embryos.
2000,
Pubmed
,
Xenbase Harland,
Formation and function of Spemann's organizer.
1997,
Pubmed Harland,
Neural induction.
2000,
Pubmed
,
Xenbase Holtfreter,
[Not Available].
1933,
Pubmed Hyvönen,
CHRD, a novel domain in the BMP inhibitor chordin, is also found in microbial proteins.
2003,
Pubmed Joly,
The ventral and posterior expression of the zebrafish homeobox gene eve1 is perturbed in dorsalized and mutant embryos.
1993,
Pubmed
,
Xenbase Kawahara,
Functional interaction of vega2 and goosecoid homeobox genes in zebrafish.
2000,
Pubmed Kawano,
Secreted antagonists of the Wnt signalling pathway.
2003,
Pubmed
,
Xenbase Kazanskaya,
The role of Xenopus dickkopf1 in prechordal plate specification and neural patterning.
2000,
Pubmed
,
Xenbase Klingensmith,
Neural induction and patterning in the mouse in the absence of the node and its derivatives.
1999,
Pubmed Kretzschmar,
Opposing BMP and EGF signalling pathways converge on the TGF-beta family mediator Smad1.
1997,
Pubmed Kuroda,
Neural induction in Xenopus: requirement for ectodermal and endomesodermal signals via Chordin, Noggin, beta-Catenin, and Cerberus.
2004,
Pubmed
,
Xenbase Lall,
Conservation and divergence in molecular mechanisms of axis formation.
2001,
Pubmed
,
Xenbase Larraín,
Proteolytic cleavage of Chordin as a switch for the dual activities of Twisted gastrulation in BMP signaling.
2001,
Pubmed
,
Xenbase Larraín,
BMP-binding modules in chordin: a model for signalling regulation in the extracellular space.
2000,
Pubmed
,
Xenbase Lemaire,
Early steps in the formation of neural tissue in ascidian embryos.
2002,
Pubmed Leung,
bozozok directly represses bmp2b transcription and mediates the earliest dorsoventral asymmetry of bmp2b expression in zebrafish.
2003,
Pubmed Leyns,
Frzb-1 is a secreted antagonist of Wnt signaling expressed in the Spemann organizer.
1997,
Pubmed
,
Xenbase London,
Expression of Epi 1, an epidermis-specific marker in Xenopus laevis embryos, is specified prior to gastrulation.
1988,
Pubmed
,
Xenbase Mao,
LDL-receptor-related protein 6 is a receptor for Dickkopf proteins.
2001,
Pubmed
,
Xenbase Mao,
Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling.
2002,
Pubmed Martyn,
The ventralized ogon mutant phenotype is caused by a mutation in the zebrafish homologue of Sizzled, a secreted Frizzled-related protein.
2003,
Pubmed Massague,
Integration of Smad and MAPK pathways: a link and a linker revisited.
2003,
Pubmed McMahon,
Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite.
1998,
Pubmed Miller,
Establishment of the dorsal-ventral axis in Xenopus embryos coincides with the dorsal enrichment of dishevelled that is dependent on cortical rotation.
1999,
Pubmed
,
Xenbase Moser,
BMPER, a novel endothelial cell precursor-derived protein, antagonizes bone morphogenetic protein signaling and endothelial cell differentiation.
2003,
Pubmed
,
Xenbase Mukhopadhyay,
Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse.
2001,
Pubmed
,
Xenbase Muñoz-Sanjuán,
Neural induction, the default model and embryonic stem cells.
2002,
Pubmed Niehrs,
Synexpression groups in eukaryotes.
1999,
Pubmed
,
Xenbase Niehrs,
The Spemann organizer and embryonic head induction.
2001,
Pubmed Niswander,
FGF-4 and BMP-2 have opposite effects on limb growth.
1993,
Pubmed Nosaka,
Mammalian twisted gastrulation is essential for skeleto-lymphogenesis.
2003,
Pubmed Oelgeschläger,
The pro-BMP activity of Twisted gastrulation is independent of BMP binding.
2003,
Pubmed
,
Xenbase 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 Pera,
Neural and head induction by insulin-like growth factor signals.
2001,
Pubmed
,
Xenbase Pera,
Integration of IGF, FGF, and anti-BMP signals via Smad1 phosphorylation in neural induction.
2003,
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 Perea-Gomez,
Nodal antagonists in the anterior visceral endoderm prevent the formation of multiple primitive streaks.
2002,
Pubmed Petryk,
The mammalian twisted gastrulation gene functions in foregut and craniofacial development.
2004,
Pubmed 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 Richard-Parpaillon,
The IGF pathway regulates head formation by inhibiting Wnt signaling in Xenopus.
2002,
Pubmed
,
Xenbase Ross,
Twisted gastrulation is a conserved extracellular BMP antagonist.
2001,
Pubmed
,
Xenbase Salic,
Sizzled: a secreted Xwnt8 antagonist expressed in the ventral marginal zone of Xenopus embryos.
1997,
Pubmed
,
Xenbase Sater,
Evidence for antagonism of BMP-4 signals by MAP kinase during Xenopus axis determination and neural specification.
2003,
Pubmed
,
Xenbase Schneider,
Beta-catenin translocation into nuclei demarcates the dorsalizing centers in frog and fish embryos.
1996,
Pubmed
,
Xenbase 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,
Mammalian BMP-1/Tolloid-related metalloproteinases, including novel family member mammalian Tolloid-like 2, have differential enzymatic activities and distributions of expression relevant to patterning and skeletogenesis.
1999,
Pubmed
,
Xenbase Scott,
Homologues of Twisted gastrulation are extracellular cofactors in antagonism of BMP signalling.
2001,
Pubmed
,
Xenbase Sharpe,
A homeobox-containing marker of posterior neural differentiation shows the importance of predetermination in neural induction.
1987,
Pubmed
,
Xenbase Shi,
Mechanisms of TGF-beta signaling from cell membrane to the nucleus.
2003,
Pubmed Spemann,
Induction of embryonic primordia by implantation of organizers from a different species. 1923.
2001,
Pubmed Stern,
Induction and initial patterning of the nervous system - the chick embryo enters the scene.
2002,
Pubmed
,
Xenbase Streit,
Neural induction. A bird's eye view.
1999,
Pubmed
,
Xenbase Takahashi,
Two novel nodal-related genes initiate early inductive events in Xenopus Nieuwkoop center.
2000,
Pubmed
,
Xenbase Tamai,
A mechanism for Wnt coreceptor activation.
2004,
Pubmed
,
Xenbase Tamai,
LDL-receptor-related proteins in Wnt signal transduction.
2000,
Pubmed
,
Xenbase Thesleff,
The role of growth factors in tooth development.
2002,
Pubmed von Ohlen,
Convergence of dorsal, dpp, and egfr signaling pathways subdivides the drosophila neuroectoderm into three dorsal-ventral columns.
2000,
Pubmed Warren,
The BMP antagonist noggin regulates cranial suture fusion.
2003,
Pubmed Weaver,
GBP binds kinesin light chain and translocates during cortical rotation in Xenopus eggs.
2003,
Pubmed
,
Xenbase Weaver,
Bmp4 and Fgf10 play opposing roles during lung bud morphogenesis.
2000,
Pubmed Weinstein,
Neural induction.
1999,
Pubmed
,
Xenbase Wessely,
Analysis of Spemann organizer formation in Xenopus embryos by cDNA macroarrays.
2004,
Pubmed
,
Xenbase Wessely,
Neural induction in the absence of mesoderm: beta-catenin-dependent expression of secreted BMP antagonists at the blastula stage in Xenopus.
2001,
Pubmed
,
Xenbase Wilson,
Neural induction: toward a unifying mechanism.
2001,
Pubmed Wilson,
Induction of epidermis and inhibition of neural fate by Bmp-4.
1995,
Pubmed
,
Xenbase Yabe,
Ogon/Secreted Frizzled functions as a negative feedback regulator of Bmp signaling.
2003,
Pubmed
,
Xenbase Yamamoto,
Nodal antagonists regulate formation of the anteroposterior axis of the mouse embryo.
2004,
Pubmed Zakin,
Inactivation of mouse Twisted gastrulation reveals its role in promoting Bmp4 activity during forebrain development.
2004,
Pubmed
,
Xenbase Zimmerman,
The Spemann organizer signal noggin binds and inactivates bone morphogenetic protein 4.
1996,
Pubmed
,
Xenbase
