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A gene regulatory network controlling the embryonic specification of endoderm

Nature volume 474, pages 635–639 (2011)Cite this article

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Abstract

Specification of endoderm is the prerequisite for gut formation in the embryogenesis of bilaterian organisms. Modern lineage labelling studies1,2,3 have shown that in the sea urchin embryo model system, descendants of the veg1 and veg2 cell lineages produce the endoderm, and that the veg2 lineage also gives rise to mesodermal cell types. It is known that Wnt/β-catenin signalling is required for endoderm specification4,5,6 and Delta/Notch signalling is required for mesoderm specification7,8,9. Some direct cis-regulatory targets of these signals have been found10,11 and various phenomenological patterns of gene expression have been observed in the pre-gastrular endomesoderm. However, no comprehensive, causal explanation of endoderm specification has been conceived for sea urchins, nor for any other deuterostome. Here we propose a model, on the basis of the underlying genomic control system, that provides such an explanation, built at several levels of biological organization. The hardwired core of the control system consists of the cis-regulatory apparatus of endodermal regulatory genes, which determine the relationship between the inputs to which these genes are exposed and their outputs. The architecture of the network circuitry controlling the dynamic process of endoderm specification then explains, at the system level, a sequence of developmental logic operations, which generate the biological process. The control system initiates non-interacting endodermal and mesodermal gene regulatory networks in veg2-derived cells and extinguishes the endodermal gene regulatory network in mesodermal precursors. It also generates a cross-regulatory network that specifies future anterior endoderm in veg2 descendants and institutes a distinct network specifying posterior endoderm in veg1-derived cells. The network model provides an explanatory framework that relates endoderm specification to the genomic regulatory code.

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Figure 1: Endodermal gene expression and perturbation matrix.
Figure 2: Separation of endoderm and mesoderm regulatory states.
Figure 3: Separation of anterior and posterior endoderm regulatory states.
Figure 4: Anterior and posterior GRNs just before gastrulation.

References

  1. Cameron, R. A., Fraser, S. E., Britten, R. J. & Davidson, E. H. Macromere cell fates during sea urchin development. Development 113, 1085–1091 (1991)

    CAS  PubMed  Google Scholar 

  2. Logan, C. Y. & McClay, D. R. The allocation of early blastomeres to the ectoderm and endoderm is variable in the sea urchin embryo. Development 124, 2213–2223 (1997)

    CAS  PubMed  Google Scholar 

  3. Ransick, A. & Davidson, E. H. Late specification of Veg1 lineages to endodermal fate in the sea urchin embryo. Dev. Biol. 195, 38–48 (1998)

    CAS  Article  Google Scholar 

  4. Byrum, C. A., Xu, R., Bince, J. M., McClay, D. R. & Wikramanayake, A. H. Blocking Dishevelled signaling in the noncanonical Wnt pathway in sea urchins disrupts endoderm formation and spiculogenesis, but not secondary mesoderm formation. Dev. Dyn. 238, 1649–1665 (2009)

    CAS  Article  Google Scholar 

  5. Logan, C. Y., Miller, J. R., Ferkowicz, M. J. & McClay, D. R. Nuclear β-catenin is required to specify vegetal cell fates in the sea urchin embryo. Development 126, 345–357 (1999)

    CAS  PubMed  Google Scholar 

  6. Wikramanayake, A. H. et al. Nuclear β-catenin-dependent Wnt8 signaling in vegetal cells of the early sea urchin embryo regulates gastrulation and differentiation of endoderm and mesodermal cell lineages. Genesis 39, 194–205 (2004)

    CAS  Article  Google Scholar 

  7. Sherwood, D. R. & McClay, D. R. LvNotch signaling mediates secondary mesenchyme specification in the sea urchin embryo. Development 126, 1703–1713 (1999)

    CAS  PubMed  Google Scholar 

  8. Sweet, H. C., Hodor, P. G. & Ettensohn, C. A. The role of micromere signaling in Notch activation and mesoderm specification during sea urchin embryogenesis. Development 126, 5255–5265 (1999)

    CAS  PubMed  Google Scholar 

  9. Sweet, H. C., Gehring, M. & Ettensohn, C. A. LvDelta is a mesoderm-inducing signal in the sea urchin embryo and can endow blastomeres with organizer-like properties. Development 129, 1945–1955 (2002)

    CAS  PubMed  Google Scholar 

  10. Ransick, A. & Davidson, E. H. cis-regulatory processing of Notch signaling input to the sea urchin glial cells missing gene during mesoderm specification. Dev. Biol. 297, 587–602 (2006)

    CAS  Article  Google Scholar 

  11. de-Leon, S. B. & Davidson, E. H. Information processing at the foxa node of the sea urchin endomesoderm specification network. Proc. Natl Acad. Sci. USA 107, 10103–10108 (2010)

    ADS  Article  Google Scholar 

  12. Howard-Ashby, M. et al. Identification and characterization of homeobox transcription factor genes in Strongylocentrotus purpuratus, and their expression in embryonic development. Dev. Biol. 300, 74–89 (2006)

    CAS  Article  Google Scholar 

  13. Howard-Ashby, M. et al. Gene families encoding transcription factors expressed in early development of Strongylocentrotus purpuratus . Dev. Biol. 300, 90–107 (2006)

    CAS  Article  Google Scholar 

  14. Materna, S. C., Howard-Ashby, M., Gray, R. F. & Davidson, E. H. The C2H2 zinc finger genes of Strongylocentrotus purpuratus and their expression in embryonic development. Dev. Biol. 300, 108–120 (2006)

    CAS  Article  Google Scholar 

  15. Rizzo, F., Fernandez-Serra, M., Squarzoni, P., Archimandritis, A. & Arnone, M. I. Identification and developmental expression of the ets gene family in the sea urchin (Strongylocentrotus purpuratus). Dev. Biol. 300, 35–48 (2006)

    CAS  Article  Google Scholar 

  16. Tu, Q., Brown, C. T., Davidson, E. H. & Oliveri, P. Sea urchin Forkhead gene family: phylogeny and embryonic expression. Dev. Biol. 300, 49–62 (2006)

    CAS  Article  Google Scholar 

  17. Peter, I. S. & Davidson, E. H. The endoderm gene regulatory network in sea urchin embryos up to mid-blastula stage. Dev. Biol. 340, 188–199 (2010)

    CAS  Article  Google Scholar 

  18. Minokawa, T., Wikramanayake, A. H. & Davidson, E. H. cis-Regulatory inputs of the wnt8 gene in the sea urchin endomesoderm network. Dev. Biol. 288, 545–558 (2005)

    CAS  Article  Google Scholar 

  19. Smith, J., Kraemer, E., Liu, H., Theodoris, C. & Davidson, E. A spatially dynamic cohort of regulatory genes in the endomesodermal gene network of the sea urchin embryo. Dev. Biol. 313, 863–875 (2008)

    CAS  Article  Google Scholar 

  20. Peter, I. S. & Davidson, E. H. Modularity and design principles in the sea urchin embryo gene regulatory network. FEBS Lett. 583, 3948–3958 (2009)

    CAS  Article  Google Scholar 

  21. Croce, J. C. & McClay, D. R. Dynamics of Delta/Notch signaling on endomesoderm segregation in the sea urchin embryo. Development 137, 83–91 (2010)

    CAS  Article  Google Scholar 

  22. Davidson, E. H. Emerging properties of animal gene regulatory networks. Nature 468, 911–920 (2010)

    ADS  CAS  Article  Google Scholar 

  23. Smith, J., Theodoris, C. & Davidson, E. H. A gene regulatory network subcircuit drives a dynamic pattern of gene expression. Science 318, 794–797 (2007)

    ADS  CAS  Article  Google Scholar 

  24. Livi, C. B. & Davidson, E. H. Regulation of spblimp1/krox1a, an alternatively transcribed isoform expressed in midgut and hindgut of the sea urchin gastrula. Gene Expr. Patterns 7, 1–7 (2007)

    CAS  Article  Google Scholar 

  25. Ransick, A. Detection of mRNA by in situ hybridization and RT-PCR. Methods Cell Biol. 74, 601–620 (2004)

    CAS  Article  Google Scholar 

  26. Oliveri, P., Tu, Q. & Davidson, E. H. Global regulatory logic for specification of an embryonic cell lineage. Proc. Natl Acad. Sci. USA 105, 5955–5962 (2008)

    ADS  CAS  Article  Google Scholar 

  27. Longabaugh, W. J., Davidson, E. H. & Bolouri, H. Visualization, documentation, analysis, and communication of large-scale gene regulatory networks. Biochim. Biophys. Acta 1789, 363–374 (2009)

    CAS  Article  Google Scholar 

  28. Rast, J. P. et al. Recovery of developmentally defined gene sets from high-density cDNA macroarrays. Dev. Biol. 228, 270–286 (2000)

    CAS  Article  Google Scholar 

  29. Materna, S. C. & Oliveri, P. A protocol for unraveling gene regulatory networks. Nature Protocols 3, 1876–1887 (2008)

    CAS  Article  Google Scholar 

  30. Revilla-i-Domingo, R., Oliveri, P. & Davidson, E. H. A missing link in the sea urchin embryo gene regulatory network: hesC and the double-negative specification of micromeres. Proc. Natl Acad. Sci. USA 104, 12383–12388 (2007)

    ADS  CAS  Article  Google Scholar 

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Acknowledgements

We acknowledge technical assistance from J. Yun, who executed much of the perturbation analysis matrix, and from A. Puszynska and E. Erkenbrack, who contributed to whole-mount in situ hybridization results. We are grateful to E. Rothenberg for a detailed critique of the manuscript. I.S.P. was the recipient of a fellowship from the Swiss National Science Foundation in the initial stages of this work. The research was supported by National Institutes of Health grant HD37105 to E.H.D.

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  1. Division of Biology, California Institute of Technology, Pasadena, California 91125, USA,

    Isabelle S. Peter & Eric H. Davidson

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  1. Isabelle S. Peter
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Contributions

This research was conceived by I.S.P. and E.H.D. and all experiments were designed and executed by I.S.P. with the assistance acknowledged above. The results were interpreted by I.S.P. and E.H.D., who also contributed jointly to the manuscript.

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Correspondence to Isabelle S. Peter or Eric H. Davidson.

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The authors declare no competing financial interests.

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Peter, I., Davidson, E. A gene regulatory network controlling the embryonic specification of endoderm. Nature 474, 635–639 (2011). https://doi.org/10.1038/nature10100

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