The establishment of spemann's organizer and patterning of the vertebrate embryo

Molecular studies have begun to unravel the sequential cell–cell signalling events that establish the dorsal–ventral, or 'back-to-belly', axis of vertebrate animals. In Xenopus and zebrafish, these events start with the movement of membrane vesicles associated with dorsal determinants. This mediates the induction of mesoderm by generating gradients of growth factors. Dorsal mesoderm then becomes a signalling centre, the Spemann's organizer, which secretes several antagonists of growth-factor signalling. Recent studies have led to new models for the regulation of cell–cell signalling during development, which may also apply to the homeostasis of adult tissues.

[1]  M. Ekker,et al.  The role of tolloid/mini fin in dorsoventral pattern formation of the zebrafish embryo. , 1999, Development.

[2]  E. L. Ferguson,et al.  Spatially Restricted Activation of the SAX Receptor by SCW Modulates DPP/TKV Signaling in Drosophila Dorsal–Ventral Patterning , 1998, Cell.

[3]  M Whitman,et al.  Endogenous patterns of TGFbeta superfamily signaling during early Xenopus development. , 2000, Development.

[4]  A. Kuroiwa,et al.  Removal of vegetal yolk causes dorsal deficencies and impairs dorsal-inducing ability of the yolk cell in zebrafish , 1999, Mechanisms of Development.

[5]  Naoto Ueno,et al.  Interaction between Wnt and TGF-β signalling pathways during formation of Spemann's organizer , 2000, Nature.

[6]  M. Kirschner,et al.  Sizzled: a secreted Xwnt8 antagonist expressed in the ventral marginal zone of Xenopus embryos. , 1997, Development.

[7]  Jian Zhang,et al.  The Role of Maternal VegT in Establishing the Primary Germ Layers in Xenopus Embryos , 1998, Cell.

[8]  R. Nusse,et al.  Mechanisms of Wnt signaling in development. , 1998, Annual review of cell and developmental biology.

[9]  Y. Sasai,et al.  Xenopus chordin: A novel dorsalizing factor activated by organizer-specific homeobox genes , 1994, Cell.

[10]  D. Melton,et al.  Xnr4: a Xenopus nodal-related gene expressed in the Spemann organizer. , 1997, Developmental biology.

[11]  E. D. De Robertis,et al.  A direct screen for secreted proteins in Xenopus embryos identifies distinct activities for the Wnt antagonists Crescent and Frzb-1 , 2000, Mechanisms of Development.

[12]  J. Brachet,et al.  An old enigma: the gray crescent of amphibian eggs. , 1977, Current topics in developmental biology.

[13]  O. Shimmi,et al.  Processing of the Drosophila Sog protein creates a novel BMP inhibitory activity. , 2000, Development.

[14]  M. Fürthauer,et al.  Equivalent genetic roles for bmp7/snailhouse and bmp2b/swirl in dorsoventral pattern formation. , 2000, Development.

[15]  Ryan M. Anderson,et al.  The organizer factors Chordin and Noggin are required for mouse forebrain development , 2000, Nature.

[16]  D. Melton,et al.  A molecular mechanism for the effect of lithium on development. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[17]  K. Hori,et al.  Erratum: New gene, nel, encoding a Mr 91 K protein with EGF-like repeats is strongly expressed in neural tissues of early stage chick embryos (Developmental Dynamics (1995) 203 (202-213)) , 1996 .

[18]  Leslie Dale,et al.  Cleavage of Chordin by Xolloid Metalloprotease Suggests a Role for Proteolytic Processing in the Regulation of Spemann Organizer Activity , 1997, Cell.

[19]  D. Kimelman,et al.  Patterning the early zebrafish by the opposing actions of bozozok and vox/vent. , 2000, Developmental biology.

[20]  Gary R. Grotendorst,et al.  Combinatorial signaling by Twisted Gastrulation and Decapentaplegic , 1997, Mechanisms of Development.

[21]  P. Polakis Wnt signaling and cancer. , 2000, Genes & development.

[22]  Ken W. Y. Cho,et al.  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, Developmental biology.

[23]  T. Bouwmeester,et al.  Cerberus is a head-inducing secreted factor expressed in the anterior endoderm of Spemann's organizer , 1996, Nature.

[24]  Carmen Birchmeier,et al.  Requirement for β-Catenin in Anterior-Posterior Axis Formation in Mice , 2000, The Journal of cell biology.

[25]  K. Anderson,et al.  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, Development.

[26]  D. Kimelman,et al.  Activation of Siamois by the Wnt pathway. , 1996, Developmental biology.

[27]  Allan Bradley,et al.  Requirement for Wnt3 in vertebrate axis formation , 1999, Nature Genetics.

[28]  R. Harland,et al.  The Spemann Organizer Signal noggin Binds and Inactivates Bone Morphogenetic Protein 4 , 1996, Cell.

[29]  A. McMahon,et al.  Genetic analysis of dorsoventral pattern formation in the zebrafish: requirement of a BMP-like ventralizing activity and its dorsal repressor. , 1996, Genes & development.

[30]  K. Kao,et al.  The entire mesodermal mantle behaves as Spemann's organizer in dorsoanterior enhanced Xenopus laevis embryos. , 1988, Developmental biology.

[31]  Smads and early developmental signaling by the TGFbeta superfamily. , 1998, Genes & development.

[32]  H. Sive,et al.  Mesoderm induction in Xenopus is a zygotic event regulated by maternal VegT via TGFbeta growth factors. , 1999, Development.

[33]  K. Hori,et al.  New gene, nel, encoding a Mr 93 K protein with EGF‐like repeats is strongly expressed in neural tissues of early stage chick embryos , 1995, Developmental dynamics : an official publication of the American Association of Anatomists.

[34]  S. Fisher,et al.  Patterning the zebrafish axial skeleton requires early chordin function , 1999, Nature Genetics.

[35]  T. Bouwmeester,et al.  The smad5 mutation somitabun blocks Bmp2b signaling during early dorsoventral patterning of the zebrafish embryo. , 1999, Development.

[36]  Carmen Birchmeier,et al.  Requirement for beta-catenin in anterior-posterior axis formation in mice. , 2000 .

[37]  D. Melton,et al.  Mixer, a homeobox gene required for endoderm development. , 1998, Science.

[38]  S. Subtelny,et al.  Determinants of spatial organization , 1979 .

[39]  L. Solnica-Krezel,et al.  The homeobox gene bozozok promotes anterior neuroectoderm formation in zebrafish through negative regulation of BMP2/4 and Wnt pathways. , 2000, Development.

[40]  F. Conlon,et al.  A primary requirement for nodal in the formation and maintenance of the primitive streak in the mouse. , 1994, Development.

[41]  M. Gates,et al.  Zebrafish organizer development and germ-layer formation require nodal-related signals , 1998, Nature.

[42]  Linda Lowe,et al.  Nodal is a novel TGF-β-like gene expressed in the mouse node during gastrulation , 1993, Nature.

[43]  T. Bouwmeester,et al.  Frzb-1 Is a Secreted Antagonist of Wnt Signaling Expressed in the Spemann Organizer , 1997, Cell.

[44]  R. Keller,et al.  Gastrulation : movements, patterns, and molecules , 1991 .

[45]  R. Ho,et al.  The nieuwkoid/dharma homeobox gene is essential for bmp2b repression in the zebrafish pregastrula. , 1999, Developmental biology.

[46]  J. Slack The heritage of experimental embryology: Hans Spemann and the organizer , 1989, Medical History.

[47]  A. Fainsod,et al.  The dorsalizing and neural inducing gene follistatin is an antagonist of BMP-4 , 1997, Mechanisms of Development.

[48]  B. Thisse,et al.  Antivin, a novel and divergent member of the TGFbeta superfamily, negatively regulates mesoderm induction. , 1999, Development.

[49]  D. Kimelman,et al.  Regulation of dorsal gene expression in Xenopus by the ventralizing homeodomain gene Vox. , 1999, Developmental biology.

[50]  M. Whitman Smads and early developmental signaling by the TGFbeta superfamily. , 1998, Genes & development.

[51]  L. Zon,et al.  The molecular nature of zebrafish swirl: BMP2 function is essential during early dorsoventral patterning. , 1997, Development.

[52]  Wei Hsu,et al.  The Mouse Fused Locus Encodes Axin, an Inhibitor of the Wnt Signaling Pathway That Regulates Embryonic Axis Formation , 1997, Cell.

[53]  E. Robertis,et al.  The evolutionarily conserved BMP-binding protein Twisted gastrulation promotes BMP signalling , 2000, Nature.

[54]  P. McCrea,et al.  Overexpression of cadherins and underexpression of β-catenin inhibit dorsal mesoderm induction in early Xenopus embryos , 1994, Cell.

[55]  L. Wolpert Developmental Biology , 1968, Nature.

[56]  H. Uchiyama,et al.  Direct binding of follistatin to a complex of bone-morphogenetic protein and its receptor inhibits ventral and epidermal cell fates in early Xenopus embryo. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[57]  J. D. Brown,et al.  Expression of a dominant-negative Wnt blocks induction of MyoD in Xenopus embryos. , 1996, Genes & development.

[58]  William C. Smith,et al.  Expression cloning of noggin, a new dorsalizing factor localized to the Spemann organizer in Xenopus embryos , 1992, Cell.

[59]  S. Ekker,et al.  The putative wnt receptor Xenopus frizzled-7 functions upstream of beta-catenin in vertebrate dorsoventral mesoderm patterning. , 2000, Development.

[60]  T. Watabe,et al.  Molecular mechanisms of Spemann's organizer formation: conserved growth factor synergy between Xenopus and mouse. , 1995, Genes & development.

[61]  T. Bouwmeester,et al.  The head inducer Cerberus is a multifunctional antagonist of Nodal, BMP and Wnt signals , 1999, Nature.

[62]  Iman H. Brivanlou,et al.  TGF-beta signals and a pattern in Xenopus laevis endodermal development. , 1996, Development.

[63]  D. Kessler,et al.  Siamois is required for formation of Spemann's organizer. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[64]  J. Rossant,et al.  A mouse cerberus/Dan-related gene family. , 1999, Developmental biology.

[65]  W. Talbot,et al.  bozozok and squint act in parallel to specify dorsal mesoderm and anterior neuroectoderm in zebrafish. , 2000, Development.

[66]  J. Emery,et al.  Dorsal-ventral patterning of the Drosophila embryo depends on a putative negative growth factor encoded by the short gastrulation gene. , 1994, Genes & development.

[67]  Y. Sasai,et al.  A common plan for dorsoventral patterning in Bilateria , 1996, Nature.

[68]  J. Gerhart,et al.  Formation and function of Spemann's organizer. , 1997, Annual review of cell and developmental biology.

[69]  K. Mizuseki,et al.  Xenopus kielin: A dorsalizing factor containing multiple chordin-type repeats secreted from the embryonic midline. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[70]  R. Moon,et al.  From cortical rotation to organizer gene expression: toward a molecular explanation of axis specification in Xenopus , 1998, BioEssays : news and reviews in molecular, cellular and developmental biology.

[71]  M. R. Dohmen,et al.  The Ultrastructure and Role of the Polar Lobe in Development of Molluscs , 1979 .

[72]  Uwe Strähle,et al.  Dynamic microtubules and specification of the zebrafish embryonic axis , 1997, Current Biology.

[73]  J. Wrana,et al.  The Xenopus Dorsalizing Factor noggin Ventralizes Drosophila Embryos by Preventing DPP from Activating Its Receptor , 1996, Cell.

[74]  Andrew P. McMahon,et al.  The zebrafish organizer requires chordino , 1997, Nature.

[75]  C. Larabell,et al.  Establishment of the Dorso-ventral Axis in Xenopus Embryos Is Presaged by Early Asymmetries in β-Catenin That Are Modulated by the Wnt Signaling Pathway , 1997, The Journal of cell biology.

[76]  E. D. De Robertis,et al.  Endodermal Nodal-related signals and mesoderm induction in Xenopus. , 2000, Development.

[77]  Ken W. Y. Cho,et al.  Production of a DPP Activity Gradient in the Early Drosophila Embryo through the Opposing Actions of the SOG and TLD Proteins , 1997, Cell.

[78]  C. Wright,et al.  The lefty-related factor Xatv acts as a feedback inhibitor of nodal signaling in mesoderm induction and L-R axis development in xenopus. , 2000, Development.

[79]  J. Gurdon,et al.  A homeobox-containing marker of posterior neural differentiation shows the importance of predetermination in neural induction , 1987, Cell.

[80]  C. Niehrs,et al.  Head induction by simultaneous repression of Bmp and Wnt signalling in Xenopus , 1997, Nature.

[81]  C. Larabell,et al.  Establishment of the Dorsal–Ventral Axis inXenopus Embryos Coincides with the Dorsal Enrichment of Dishevelled That Is Dependent on Cortical Rotation , 1999, The Journal of cell biology.

[82]  P. Lemaire,et al.  A two-step model for the fate determination of presumptive endodermal blastomeres in Xenopus embryos , 1999, Current Biology.

[83]  Yoshiki Sasai,et al.  A conserved system for dorsal-ventral patterning in insects and vertebrates involving sog and chordin , 1995, Nature.

[84]  J. Gurdon,et al.  The heritage of experimental embryology: Hans Spemann and the organizer by Viktor Hamburger, Oxford University Press, 1988. £22.50/$29.95 (196 pages) ISBN 0 19505 110 6 , 1989, Trends in Neurosciences.

[85]  J. Gerhart,et al.  Organizing the Xenopus Organizer , 1991 .

[86]  Michael Levine,et al.  Local inhibition and long-range enhancement of Dpp signal transduction by Sog , 1999, Nature.

[87]  H. Steinbeisser,et al.  β-catenin translocation into nuclei demarcates the dorsalizing centers in frog and fish embryos , 1996, Mechanisms of Development.

[88]  A. Schier,et al.  Nodal signalling in vertebrate development , 2000, Nature.

[89]  J. Heasman Patterning the Xenopus blastula. , 1997, Development.

[90]  Ken W. Y. Cho,et al.  The Xenopus homeobox gene twin mediates Wnt induction of goosecoid in establishment of Spemann's organizer. , 1997, Development.

[91]  William C. Smith,et al.  Direct neural induction and selective inhibition of mesoderm and epidermis inducers by Xnr3. , 1997, Development.

[92]  J. Gerhart,et al.  High-frequency twinning of Xenopus laevis embryos from eggs centrifuged before first cleavage. , 1986, Developmental biology.

[93]  M. Hosobuchi,et al.  Maternal beta-catenin establishes a 'dorsal signal' in early Xenopus embryos. , 1996, Development.

[94]  L. Attisano,et al.  Association of Smads with lymphoid enhancer binding factor 1/T cell-specific factor mediates cooperative signaling by the transforming growth factor-beta and wnt pathways. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[95]  D. J. Olson,et al.  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, Development.

[96]  Y. Sasai,et al.  Dorsoventral Patterning in Xenopus: Inhibition of Ventral Signals by Direct Binding of Chordin to BMP-4 , 1996, Cell.

[97]  Sangbin Park,et al.  Interpretation of a BMP Activity Gradient in Drosophila Embryos Depends on Synergistic Signaling by Two Type I Receptors, SAX and TKV , 1998, Cell.

[98]  P. Lemaire,et al.  Animal and vegetal pole cells of early Xenopus embryos respond differently to maternal dorsal determinants: implications for the patterning of the organiser. , 1997, Development.

[99]  C. Niehrs,et al.  The Xvent-2 homeobox gene is part of the BMP-4 signalling pathway controling dorsoventral patterning of Xenopus mesoderm , 1996 .

[100]  Iman H. Brivanlou,et al.  TGF-β signals and a prepattern in Xenopus laevis endodermal development , 1996 .

[101]  F. Luyten,et al.  Frzb, a Secreted Protein Expressed in the Spemann Organizer, Binds and Inhibits Wnt-8 , 1997, Cell.

[102]  W. Talbot,et al.  Mouse Lefty2 and zebrafish antivin are feedback inhibitors of nodal signaling during vertebrate gastrulation. , 1999, Molecular cell.

[103]  C. Niehrs,et al.  Synexpression groups in eukaryotes , 1999, Nature.

[104]  G. Kolle,et al.  CRIM1, a novel gene encoding a cysteine-rich repeat protein, is developmentally regulated and implicated in vertebrate CNS development and organogenesis , 2000, Mechanisms of Development.

[105]  S. Germain,et al.  Homeodomain and winged-helix transcription factors recruit activated Smads to distinct promoter elements via a common Smad interaction motif. , 2000, Genes & development.

[106]  D. Keene,et al.  Type IIA Procollagen Containing the Cysteine-rich Amino Propeptide Is Deposited in the Extracellular Matrix of Prechondrogenic Tissue and Binds to TGF-β1 and BMP-2 , 1999, The Journal of cell biology.

[107]  C. Niehrs,et al.  Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction , 1998, Nature.

[108]  E. D. De Robertis,et al.  BMP-binding modules in chordin: a model for signalling regulation in the extracellular space. , 2000, Development.

[109]  C. Larabell,et al.  Microtubule-mediated transport of organelles and localization of beta-catenin to the future dorsal side of Xenopus eggs. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[110]  R. Beddington,et al.  Wnt signaling in Xenopus embryos inhibits bmp4 expression and activates neural development. , 1999, Genes & development.

[111]  J. Marsh,et al.  Dorsal midline fate in Drosophila embryos requires twisted gastrulation, a gene encoding a secreted protein related to human connective tissue growth factor. , 1994, Genes & development.

[112]  Hans Clevers,et al.  XTcf-3 Transcription Factor Mediates β-Catenin-Induced Axis Formation in Xenopus Embryos , 1996, Cell.

[113]  J. Smith,et al.  Nodal-related signals induce axial mesoderm and dorsalize mesoderm during gastrulation. , 1995, Development.

[114]  E. Ober,et al.  Signals from the yolk cell induce mesoderm, neuroectoderm, the trunk organizer, and the notochord in zebrafish. , 1999, Developmental biology.

[115]  Y. Saijoh,et al.  Left–right asymmetric expression of the TGFβ-family member lefty in mouse embryos , 1996, Nature.

[116]  C. Wylie,et al.  Beta-catenin signaling activity dissected in the early Xenopus embryo: a novel antisense approach. , 2000, Developmental biology.