A genetic regulatory network for Xenopus mesendoderm formation.

We have constructed a genetic regulatory network (GRN) summarising the functional relationships between the transcription factors (TFs) and embryonic signals involved in Xenopus mesendoderm formation. It is supported by a relational database containing the experimental evidence and both are available in interactive form via the World Wide Web. This network highlights areas for further study and provides a framework for systematic interrogation of new data. Comparison with the equivalent network for the sea urchin identifies conserved features of the deuterostome ancestral pathway, including positive feedback loops, GATA factors, SoxB, Brachyury and a previously underemphasised role for beta-catenin. In contrast, some features central to one species have not yet been found in the other, for example, Krox and Otx in sea urchin, and Mix and Nodal in Xenopus. Such differences may represent evolved features or may eventually be resolved. For example, in Xenopus, Nodal-related genes are positively regulated by beta-catenin and at least one of them is repressed by Sox3, as is the uncharacterised early signal (ES) inducing endomesoderm in the sea urchin, suggesting that ES may be a Nodal-like TGF-beta. Wider comparisons of such networks will inform our understanding of developmental evolution.

[1]  R. Patient,et al.  A role for GATA5 in Xenopus endoderm specification. , 2000, Development.

[2]  M. L. King,et al.  The maternally expressed zebrafish T-box gene eomesodermin regulates organizer formation , 2003, Development.

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

[4]  R. Harland,et al.  A nodal-related gene defines a physical and functional domain within the Spemann organizer , 1995, Cell.

[5]  R. Shivdasani.  Molecular regulation of vertebrate early endoderm development. , 2002, Developmental biology.

[6]  R. Shivdasani,et al.  Action of the Caenorhabditis elegans GATA factor END-1 in Xenopus suggests that similar mechanisms initiate endoderm development in ecdysozoa and vertebrates. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[7]  E. Davidson,et al.  Origins of immunity: transcription factors and homologues of effector genes of the vertebrate immune system expressed in sea urchin coelomocytes , 1999, Immunogenetics.

[8]  U. Technau,et al.  Origin and evolution of endoderm and mesoderm. , 2003, The International journal of developmental biology.

[9]  P. S. Klein,et al.  β-Catenin/Tcf-regulated transcription prior to the midblastula transition , 2002, Development.

[10]  E. Li,et al.  Smad2 role in mesoderm formation, left–right patterning and craniofacial development , 1998, Nature.

[11]  J. Smith,et al.  A screen for targets of the Xenopus T-box gene Xbra , 2000, Mechanisms of Development.

[12]  J. McGhee,et al.  The GATA family (vertebrates and invertebrates). , 2002, Current opinion in genetics & development.

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

[14]  Paul Richardson,et al.  The Draft Genome of Ciona intestinalis: Insights into Chordate and Vertebrate Origins , 2002, Science.

[15]  A. Schier,et al.  Mixer/Bon and FoxH1/Sur have overlapping and divergent roles in Nodal signaling and mesendoderm induction , 2003, Development.

[16]  J. Gurdon,et al.  eFGF and its mode of action in the community effect during Xenopus myogenesis. , 2001, Development.

[17]  H. Woodland,et al.  Mode of action of VegT in mesoderm and endoderm formation. , 1999, Development.

[18]  D. Houston,et al.  A novel role for a nodal-related protein; Xnr3 regulates convergent extension movements via the FGF receptor , 2003, Development.

[19]  P. D. Vize,et al.  DNA sequences mediating the transcriptional response of the Mix.2 homeobox gene to mesoderm induction. , 1996, Developmental biology.

[20]  M. Levine,et al.  Characterization of a maternal T-Box gene in Ciona intestinalis. , 2000, Developmental biology.

[21]  E. Boncinelli,et al.  The Xenopus homologue of Otx2 is a maternal homeobox gene that demarcates and specifies anterior body regions. , 1995, Development.

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

[23]  O. Destrée,et al.  Lef-1 and Tcf-3 Transcription Factors Mediate Tissue-Specific Wnt Signaling during Xenopus Development , 2002, Current Biology.

[24]  H. Yamaguchi,et al.  A PEA3 site flanked by SP1, SP4, and GATA sites positively regulates the differentiation-dependent expression of Brachyury in embryonal carcinoma P19 cells. , 1999, Biochemical and biophysical research communications.

[25]  M. Asashima,et al.  Cloning a novel developmental regulating gene, Xotx5: Its potential role in anterior formation in Xenopus laevis , 2000, Development, growth & differentiation.

[26]  R. Penzel,et al.  Characterization and early embryonic expression of a neural specific transcription factor xSOX3 in Xenopus laevis. , 1997, The International journal of developmental biology.

[27]  J. Smith,et al.  Determinants of T box protein specificity. , 2001, Development.

[28]  William R. Atchley,et al.  Molecular Evolution of the GATA Family of Transcription Factors: Conservation Within the DNA-Binding Domain , 2000, Journal of Molecular Evolution.

[29]  Patterning in vertebrate development , 2003 .

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

[31]  M. Klymkowsky,et al.  The β-catenin/VegT-regulated early zygotic gene Xnr5 is a direct target of SOX3 regulation , 2003, Development.

[32]  R. Angerer,et al.  SpSoxB1, a maternally encoded transcription factor asymmetrically distributed among early sea urchin blastomeres. , 1999, Development.

[33]  D. Kimelman,et al.  Vertebrate mesendoderm induction and patterning. , 2000, Current opinion in genetics & development.

[34]  Sudhir Kumar,et al.  MEGA2: molecular evolutionary genetics analysis software , 2001, Bioinform..

[35]  J. Smith,et al.  Bix1, a direct target of Xenopus T-box genes, causes formation of ventral mesoderm and endoderm. , 1998, Development.

[36]  N. Satoh,et al.  T-brain homologue (HpTb) is involved in the archenteron induction signals of micromere descendant cells in the sea urchin embryo. , 2002, Development.

[37]  P. Lemaire,et al.  A novel Xenopus mix-like gene milk involved in the control of the endomesodermal fates. , 1998, Development.

[38]  Shuji Takahashi,et al.  Multiple nodal-related genes act coordinately in Xenopus embryogenesis. , 2002, Developmental biology.

[39]  J. Smith,et al.  Interference with brachyury function inhibits convergent extension, causes apoptosis, and reveals separate requirements in the FGF and activin signalling pathways. , 1999, Developmental biology.

[40]  M. Asashima,et al.  Two novel nodal-related genes initiate early inductive events in Xenopus Nieuwkoop center. , 2000, Development.

[41]  L. Zon,et al.  Cloning of Mix-related homeodomain proteins using fast retrieval of gel shift activities, (FROGS), a technique for the isolation of DNA-binding proteins. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[42]  M. Beltrame,et al.  Cloning and expression pattern of a zebrafish homolog of forkhead activin signal transducer (FAST), a transcription factor mediating Nodal-related signals , 2000, Mechanisms of Development.

[43]  C. Niehrs,et al.  The zinc finger gene Xblimp1 controls anterior endomesodermal cell fate in Spemann's organizer , 1999, The EMBO journal.

[44]  R. Patient,et al.  Mesendoderm An Ancient Germ Layer? , 2001, Cell.

[45]  D. Kessler,et al.  VegT activation of Sox17 at the midblastula transition alters the response to nodal signals in the vegetal endoderm domain. , 2001, Developmental biology.

[46]  Eric H Davidson,et al.  A provisional regulatory gene network for specification of endomesoderm in the sea urchin embryo. , 2002, Developmental biology.

[47]  L. Hood,et al.  A Genomic Regulatory Network for Development , 2002, Science.

[48]  Le A. Trinh,et al.  The Mix family homeodomain gene bonnie and clyde functions with other components of the Nodal signaling pathway to regulate neural patterning in zebrafish , 2003, Development.

[49]  K. Schaible,et al.  The roles of three signaling pathways in the formation and function of the Spemann Organizer. , 2002, Development.

[50]  J. Smith,et al.  Goosecoid and mix.1 repress Brachyury expression and are required for head formation in Xenopus. , 1999, Development.

[51]  E. Davidson,et al.  Cell type specification during sea urchin development. , 1991, Trends in genetics : TIG.

[52]  A. Schohl,et al.  A role for maternal β‐catenin in early mesoderm induction in Xenopus , 2003 .

[53]  P. Lemaire,et al.  A role for the vegetally expressed Xenopus gene Mix.1 in endoderm formation and in the restriction of mesoderm to the marginal zone. , 1998, Development.

[54]  Ken W. Y. Cho,et al.  Nodal signaling in Xenopus gastrulae is cell-autonomous and patterned by beta-catenin. , 2003, Developmental biology.

[55]  J. Smith,et al.  Direct and indirect regulation of derrière, a Xenopus mesoderm-inducing factor, by VegT. , 2002, Development.

[56]  C. Wylie,et al.  Maternal VegT is the initiator of a molecular network specifying endoderm in Xenopus laevis. , 2001, Development.

[57]  H. Woodland,et al.  VegT induces endoderm by a self-limiting mechanism and by changing the competence of cells to respond to TGF-beta signals. , 2003, Developmental biology.

[58]  E R LaVallie,et al.  derrière: a TGF-beta family member required for posterior development in Xenopus. , 1999, Development.

[59]  H. Kawanishi,et al.  HrNodal, the ascidian nodal-related gene, is expressed in the left side of the epidermis, and lies upstream of HrPitx , 2002, Development Genes and Evolution.

[60]  E. Davidson,et al.  Developmental gene regulatory network architecture across 500 million years of echinoderm evolution , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[61]  M. Rex,et al.  Multiple interactions between maternally-activated signalling pathways control Xenopus nodal-related genes. , 2002, The International journal of developmental biology.

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

[63]  J. Smith,et al.  Bix4 is activated directly by VegT and mediates endoderm formation in Xenopus development. , 1999, Development.

[64]  F. Rosa.  Mix.1, a homeobox mRNA inducible by mesoderm inducers, is expressed mostly in the presumptive endodermal cells of Xenopus embryos , 1989, Cell.

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

[66]  J. Smith,et al.  Evolution of Brachyury proteins: identification of a novel regulatory domain conserved within Bilateria. , 2003, Developmental biology.

[67]  J. Smith,et al.  Mesoderm formation in response to Brachyury requires FGF signalling , 1995, Current Biology.

[68]  P. Lemaire,et al.  The homeobox gene Siamois is a target of the Wnt dorsalisation pathway and triggers organiser activity in the absence of mesoderm. , 1996, Development.