Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 1 March 2002:
Vol. 295. no. 5560, pp. 1669 - 1678
DOI: 10.1126/science.1069883
Prev | Table of Contents | Next

Review

A Genomic Regulatory Network for Development

Eric H. Davidson,1* Jonathan P. Rast,1 Paola Oliveri,1 Andrew Ransick,1 Cristina Calestani,1 Chiou-Hwa Yuh,1 Takuya Minokawa,1 Gabriele Amore,1 Veronica Hinman,1 César Arenas-Mena,1 Ochan Otim,1 C. Titus Brown,1 Carolina B. Livi,1 Pei Yun Lee,1 Roger Revilla,1 Alistair G. Rust,2dagger Zheng jun Pan,2ddagger Maria J. Schilstra,2 Peter J. C. Clarke,2 Maria I. Arnone,3 Lee Rowen,4 R. Andrew Cameron,1 David R. McClay,5 Leroy Hood,4 Hamid Bolouri2

Development of the body plan is controlled by large networks of regulatory genes. A gene regulatory network that controls the specification of endoderm and mesoderm in the sea urchin embryo is summarized here. The network was derived from large-scale perturbation analyses, in combination with computational methodologies, genomic data, cis-regulatory analysis, and molecular embryology. The network contains over 40 genes at present, and each node can be directly verified at the DNA sequence level by cis-regulatory analysis. Its architecture reveals specific and general aspects of development, such as how given cells generate their ordained fates in the embryo and why the process moves inexorably forward in developmental time.

1 Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
2 Science and Technology Research Centre, University of Hertfordshire, AL10 9AB, UK.
3 Stazione Zoologica Anton Dohrn, 80121 Naples, Italy.
4 Institute for Systems Biology, Seattle, WA 98105, USA.
5 Department of Zoology, Duke University, Durham, NC 27708-0325, USA.
*   To whom correspondence should be addressed. E-mail: davidson{at}caltech.edu

dagger    Present address: European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB101 1SD, UK.

ddagger    Present address: Altera European Technology Centre, Holmers Farm Way, High Wycombe, Buckinghamshire HP12 4XF, UK.

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Cross-species de novo identification of cis-regulatory modules with GibbsModule: Application to gene regulation in embryonic stem cells.
D. Xie, J. Cai, N.-Y. Chia, H. H. Ng, and S. Zhong (2008)
Genome Res. 18, 1325-1335
   Abstract »    Full Text »    PDF »
LvNumb works synergistically with Notch signaling to specify non-skeletal mesoderm cells in the sea urchin embryo.
R. C. Range, T. D. Glenn, E. Miranda, and D. R. McClay (2008)
Development 135, 2445-2454
   Abstract »    Full Text »    PDF »
Comparative genomics supports a deep evolutionary origin for the large, four-module transcriptional mediator complex.
H.-M. Bourbon (2008)
Nucleic Acids Res. 36, 3993-4008
   Abstract »    Full Text »    PDF »
The Transcription/Migration Interface in Heart Precursors of Ciona intestinalis.
L. Christiaen, B. Davidson, T. Kawashima, W. Powell, H. Nolla, K. Vranizan, and M. Levine (2008)
Science 320, 1349-1352
   Abstract »    Full Text »    PDF »
From the Cover: Feature Article: Global regulatory logic for specification of an embryonic cell lineage.
P. Oliveri, Q. Tu, and E. H. Davidson (2008)
PNAS 105, 5955-5962
   Abstract »    Full Text »    PDF »
Intrinsic noise, dissipation cost, and robustness of cellular networks: The underlying energy landscape of MAPK signal transduction.
S. Lapidus, B. Han, and J. Wang (2008)
PNAS 105, 6039-6044
   Abstract »    Full Text »    PDF »
Convergence of a head-field selector Otx2 and Notch signaling: a mechanism for lens specification.
H. Ogino, M. Fisher, and R. M. Grainger (2008)
Development 135, 249-258
   Abstract »    Full Text »    PDF »
A Gene Regulatory Network Subcircuit Drives a Dynamic Pattern of Gene Expression.
J. Smith, C. Theodoris, and E. H. Davidson (2007)
Science 318, 794-797
   Abstract »    Full Text »    PDF »
Expression of a Tumor-Related Gene Network Increases in the Mammalian Hypothalamus at the Time of Female Puberty.
C. L. Roth, C. Mastronardi, A. Lomniczi, H. Wright, R. Cabrera, A. E. Mungenast, S. Heger, H. Jung, C. Dubay, and S. R. Ojeda (2007)
Endocrinology 148, 5147-5161
   Abstract »    Full Text »    PDF »
Temporal ChIP-on-chip reveals Biniou as a universal regulator of the visceral muscle transcriptional network.
J. S. Jakobsen, M. Braun, J. Astorga, E. H. Gustafson, T. Sandmann, M. Karzynski, P. Carlsson, and E. E.M. Furlong (2007)
Genes & Dev. 21, 2448-2460
   Abstract »    Full Text »    PDF »
Current progress in network research: toward reference networks for key model organisms.
B. S. Srinivasan, N. H. Shah, J. A. Flannick, E. Abeliuk, A. F. Novak, and S. Batzoglou (2007)
Brief Bioinform 8, 318-332
   Abstract »    Full Text »    PDF »
Gene regulatory networks and developmental plasticity in the early sea urchin embryo: alternative deployment of the skeletogenic gene regulatory network.
C. A. Ettensohn, C. Kitazawa, M. S. Cheers, J. D. Leonard, and T. Sharma (2007)
Development 134, 3077-3087
   Abstract »    Full Text »    PDF »
A missing link in the sea urchin embryo gene regulatory network: hesC and the double-negative specification of micromeres.
R. Revilla-i-Domingo, P. Oliveri, and E. H. Davidson (2007)
PNAS 104, 12383-12388
   Abstract »    Full Text »    PDF »
Localized VEGF signaling from ectoderm to mesenchyme cells controls morphogenesis of the sea urchin embryo skeleton.
L. Duloquin, G. Lhomond, and C. Gache (2007)
Development 134, 2293-2302
   Abstract »    Full Text »    PDF »
Quantifying Robustness and Dissipation Cost of Yeast Cell Cycle Network: The Funneled Energy Landscape Perspectives.
B. Han and J. Wang (2007)
Biophys. J. 92, 3755-3763
   Abstract »    Full Text »    PDF »
Colloquium Papers: Between "design" and "bricolage": Genetic networks, levels of selection, and adaptive evolution.
A. S. Wilkins (2007)
PNAS 104, 8590-8596
   Abstract »    Full Text »    PDF »
Getting connected: analysis and principles of biological networks.
X. Zhu, M. Gerstein, and M. Snyder (2007)
Genes & Dev. 21, 1010-1024
   Abstract »    Full Text »    PDF »
Combinatorial transcriptional control of the lactose operon of Escherichia coli.
T. Kuhlman, Z. Zhang, M. H. Saier Jr., and T. Hwa (2007)
PNAS 104, 6043-6048
   Abstract »    Full Text »    PDF »
The Snail repressor is required for PMC ingression in the sea urchin embryo.
S.-Y. Wu and D. R. McClay (2007)
Development 134, 1061-1070
   Abstract »    Full Text »    PDF »
Flowering and determinacy in Arabidopsis.
R. Sablowski (2007)
J. Exp. Bot. 58, 899-907
   Abstract »    Full Text »    PDF »
A core transcriptional network for early mesoderm development in Drosophila melanogaster.
T. Sandmann, C. Girardot, M. Brehme, W. Tongprasit, V. Stolc, and E. E.M. Furlong (2007)
Genes & Dev. 21, 436-449
   Abstract »    Full Text »    PDF »
Embryo stability and vulnerability in an always changing world.
A. Hamdoun and D. Epel (2007)
PNAS 104, 1745-1750
   Abstract »    Full Text »    PDF »
The SCL transcriptional network and BMP signaling pathway interact to regulate RUNX1 activity.
J. E. Pimanda, I. J. Donaldson, M. F. T. R. de Bruijn, S. Kinston, K. Knezevic, L. Huckle, S. Piltz, J.-R. Landry, A. R. Green, D. Tannahill, et al. (2007)
PNAS 104, 840-845
   Abstract »    Full Text »    PDF »
Deletion of the Ttf1 Gene in Differentiated Neurons Disrupts Female Reproduction without Impairing Basal Ganglia Function.
C. Mastronardi, G. G. Smiley, J. Raber, T. Kusakabe, A. Kawaguchi, V. Matagne, A. Dietzel, S. Heger, A. E. Mungenast, R. Cabrera, et al. (2006)
J. Neurosci. 26, 13167-13179
   Abstract »    Full Text »    PDF »
Unraveling transcription regulatory networks by protein-DNA and protein-protein interaction mapping.
A. J.M. Walhout (2006)
Genome Res. 16, 1445-1454
   Abstract »    Full Text »    PDF »
Deciphering the Underlying Mechanism of Specification and Differentiation: The Sea Urchin Gene Regulatory Network.
S. Ben-Tabou de-Leon and E. H. Davidson (2006)
Sci. STKE 2006, pe47
   Abstract »    Full Text »    PDF »
The sea urchin genome: where will it lead us?.
E. H. Davidson (2006)
Science 314, 939-940
   Abstract »    Full Text »    PDF »
The Genome of the Sea Urchin Strongylocentrotus purpuratus.
Sea Urchin Genome Sequencing Consortium, E. Sodergren, G. M. Weinstock, E. H Davidson, R. A. Cameron, R. A. Gibbs, R. C. Angerer, L. M. Angerer, M. I. Arnone, D. R. Burgess, et al. (2006)
Science 314, 941-952
   Abstract »    Full Text »    PDF »
Zfp206 regulates ES cell gene expression and differentiation.
W. Zhang, E. Walker, O. J. Tamplin, J. Rossant, W. L. Stanford, and T. R. Hughes (2006)
Nucleic Acids Res. 34, 4780-4790
   Abstract »    Full Text »    PDF »
A dynamic expression survey identifies transcription factors relevant in mouse digestive tract development.
M. Y. Choi, A. I. Romer, M. Hu, M. Lepourcelet, A. Mechoor, A. Yesilaltay, M. Krieger, P. A. Gray, and R. A. Shivdasani (2006)
Development 133, 4119-4129
   Abstract »    Full Text »    PDF »
A Brief History of Systems Biology: "Every object that biology studies is a system of systems." Francois Jacob (1974)..
A. Trewavas (2006)
PLANT CELL 18, 2420-2430
   Full Text »    PDF »
Computational identification of transcriptional regulatory elements in DNA sequence.
D. GuhaThakurta (2006)
Nucleic Acids Res. 34, 3585-3598
   Abstract »    Full Text »    PDF »
A Network of Local and Redundant Gene Regulation Governs Arabidopsis Seed Maturation.
A. To, C. Valon, G. Savino, J. Guilleminot, M. Devic, J. Giraudat, and F. Parcy (2006)
PLANT CELL 18, 1642-1651
   Abstract »    Full Text »    PDF »
Specification of ectoderm restricts the size of the animal plate and patterns neurogenesis in sea urchin embryos.
S. Yaguchi, J. Yaguchi, and R. D. Burke (2006)
Development 133, 2337-2346
   Abstract »    Full Text »    PDF »
Regulatory blueprint for a chordate embryo..
K. S. Imai, M. Levine, N. Satoh, and Y. Satou (2006)
Science 312, 1183-1187
   Abstract »    Full Text »    PDF »
Ancient duplicated conserved noncoding elements in vertebrates: A genomic and functional analysis.
G. K. McEwen, A. Woolfe, D. Goode, T. Vavouri, H. Callaway, and G. Elgar (2006)
Genome Res. 16, 451-465
   Abstract »    Full Text »    PDF »
Inference of gene regulatory networks and compound mode of action from time course gene expression profiles.
M. Bansal, G. D. Gatta, and D. di Bernardo (2006)
Bioinformatics 22, 815-822
   Abstract »    Full Text »    PDF »
Bayesian sparse hidden components analysis for transcription regulation networks.
C. Sabatti and G. M. James (2006)
Bioinformatics 22, 739-746
   Abstract »    Full Text »    PDF »
Studying statistical properties of regulatory DNA sequences, and their use in predicting regulatory regions in the eukaryotic genomes.
I. Abnizova and W. R. Gilks (2006)
Brief Bioinform 7, 48-54
   Abstract »    Full Text »    PDF »
Minireview: The Neuroendocrine Regulation of Puberty: Is the Time Ripe for a Systems Biology Approach?.
S. R. Ojeda, A. Lomniczi, C. Mastronardi, S. Heger, C. Roth, A.-S. Parent, V. Matagne, and A. E. Mungenast (2006)
Endocrinology 147, 1166-1174
   Abstract »    Full Text »    PDF »
Differential transcriptional response to nonassociative and associative components of classical fear conditioning in the amygdala and hippocampus.
M. B. Keeley, M. A. Wood, C. Isiegas, J. Stein, K. Hellman, S. Hannenhalli, and T. Abel (2006)
Learn. Mem. 13, 135-142
   Abstract »    Full Text »    PDF »
Gene Regulatory Networks and the Evolution of Animal Body Plans.
E. H. Davidson and D. H. Erwin (2006)
Science 311, 796-800
   Abstract »    Full Text »    PDF »
Frizzled5/8 is required in secondary mesenchyme cells to initiate archenteron invagination during sea urchin development.
J. Croce, L. Duloquin, G. Lhomond, D. R. McClay, and C. Gache (2006)
Development 133, 547-557
   Abstract »    Full Text »    PDF »
Calcium at Fertilization and in Early Development.
M. Whitaker (2006)
Physiol Rev 86, 25-88
   Abstract »    Full Text »    PDF »
p38 MAPK is essential for secondary axis specification and patterning in sea urchin embryos.
C. A. Bradham and D. R. McClay (2006)
Development 133, 21-32
   Abstract »    Full Text »    PDF »
Absolute rate theories of epigenetic stability.
A. M. Walczak, J. N. Onuchic, and P. G. Wolynes (2005)
PNAS 102, 18926-18931
   Abstract »    Full Text »    PDF »
Topology of biological networks and reliability of information processing.
K. Klemm and S. Bornholdt (2005)
PNAS 102, 18414-18419
   Abstract »    Full Text »    PDF »
Teaching Systems Biology: An Active-learning Approach.
A. Kumar (2005)
CBE Life Sci Educ 4, 323-329
   Abstract »    Full Text »    PDF »
Xenomics.
E. Amaya (2005)
Genome Res. 15, 1683-1691
   Abstract »    Full Text »    PDF »
Functional Interaction between Two Transcription Factors Involved in the Developmental Regulation of a Small Heat Stress Protein Gene Promoter.
J. Diaz-Martin, C. Almoguera, P. Prieto-Dapena, J. M. Espinosa, and J. Jordano (2005)
Plant Physiology 139, 1483-1494
   Abstract »    Full Text »    PDF »
Fli1, Elf1, and Ets1 regulate the proximal promoter of the LMO2 gene in endothelial cells.
J.-R. Landry, S. Kinston, K. Knezevic, I. J. Donaldson, A. R. Green, and B. Gottgens (2005)
Blood 106, 2680-2687
   Abstract »    Full Text »    PDF »
Deconvolution of a Complex Target Using DNA Aptamers.
S. Fitter and R. James (2005)
J. Biol. Chem. 280, 34193-34201
   Abstract »    Full Text »    PDF »
Systems biology in the cell nucleus.
S. Gorski and T. Misteli (2005)
J. Cell Sci. 118, 4083-4092
   Abstract »    Full Text »    PDF »
Applying GIFT, a Gene Interactions Finder in Text, to fly literature.
N. Domedel-Puig and L. Wernisch (2005)
Bioinformatics 21, 3582-3583
   Abstract »    Full Text »    PDF »
An evolutionary constraint: Strongly disfavored class of change in DNA sequence during divergence of cis-regulatory modules.
R. A. Cameron, S. H. Chow, K. Berney, T.-Y. Chiu, Q.-A. Yuan, A. Kramer, A. Helguero, A. Ransick, M. Yun, and E. H. Davidson (2005)
PNAS 102, 11769-11774
   Abstract »    Full Text »    PDF »
Constructing transcriptional regulatory networks.
A. Blais and B. D. Dynlacht (2005)
Genes & Dev. 19, 1499-1511
   Abstract »    Full Text »    PDF »
VisANT: data-integrating visual framework for biological networks and modules.
Z. Hu, J. Mellor, J. Wu, T. Yamada, D. Holloway, and C. DeLisi (2005)
Nucleic Acids Res. 33, W352-W357
   Abstract »    Full Text »    PDF »
CisMols Analyzer: identification of compositionally similar cis-element clusters in ortholog conserved regions of coordinately expressed genes.
A. G. Jegga, A. Gupta, S. Gowrisankar, M. A. Deshmukh, S. Connolly, K. Finley, and B. J. Aronow (2005)
Nucleic Acids Res. 33, W408-W411
   Abstract »    Full Text »    PDF »
Seawi--a sea urchin piwi/argonaute family member is a component of MT-RNP complexes.
A. J. RODRIGUEZ, S. A. SEIPEL, D. R. HAMILL, D. P. ROMANCINO, M. DI CARLO, K. A. SUPRENANT, and E. M. BONDER (2005)
RNA 11, 646-656
   Abstract »    Full Text »    PDF »
Balancing protein similarity and gene co-expression reveals new links between genetic conservation and developmental diversity in invertebrates.
C. Lefebvre, J.-C. Aude, E. Glemet, and C. Neri (2005)
Bioinformatics 21, 1550-1558
   Abstract »    Full Text »    PDF »
From the Cover@;DELIM@;Gene Regulatory Networks Special Feature: Gene regulatory networks for development.
M. Levine and E. H. Davidson (2005)
PNAS 102, 4936-4942
   Abstract »    Full Text »    PDF »
Gene Regulatory Networks Special Feature: Xenopus as a model system to study transcriptional regulatory networks.
T. Koide, T. Hayata, and K. W. Y. Cho (2005)
PNAS 102, 4943-4948
   Abstract »    Full Text »    PDF »
Gene Regulatory Networks Special Feature: Logic functions of the genomic cis-regulatory code.
S. Istrail and E. H. Davidson (2005)
PNAS 102, 4954-4959
   Abstract »    Full Text »    PDF »
Meeting Report: The Future and Limits of Systems Biology.
E. Werner (2005)
Sci. STKE 2005, pe16
   Abstract »    Full Text »    PDF »
Making very similar embryos with divergent genomes: conservation of regulatory mechanisms of Otx between the ascidians Halocynthia roretzi and Ciona intestinalis.
I. Oda-Ishii, V. Bertrand, I. Matsuo, P. Lemaire, and H. Saiga (2005)
Development 132, 1663-1674
   Abstract »    Full Text »    PDF »
Gene Regulation at the Single-Cell Level.
N. Rosenfeld, J. W. Young, U. Alon, P. S. Swain, and M. B. Elowitz (2005)
Science 307, 1962-1965
   Abstract »    Full Text »    PDF »
Ultrasensitivity and noise propagation in a synthetic transcriptional cascade.
S. Hooshangi, S. Thiberge, and R. Weiss (2005)
PNAS 102, 3581-3586
   Abstract »    Full Text »    PDF »
Genome-wide identification of cis-regulatory sequences controlling blood and endothelial development.
I. J. Donaldson, M. Chapman, S. Kinston, J. R. Landry, K. Knezevic, S. Piltz, N. Buckley, A. R. Green, and B. Gottgens (2005)
Hum. Mol. Genet. 14, 595-601
   Abstract »    Full Text »    PDF »
SoxB1 downregulation in vegetal lineages of sea urchin embryos is achieved by both transcriptional repression and selective protein turnover.
L. M. Angerer, L. A. Newman, and R. C. Angerer (2005)
Development 132, 999-1008
   Abstract »    Full Text »    PDF »
Transcriptional program controlled by the floral homeotic gene AGAMOUS during early organogenesis.
C. Gomez-Mena, S. de Folter, M. M. R. Costa, G. C. Angenent, and R. Sablowski (2005)
Development 132, 429-438
   Abstract »    Full Text »    PDF »
The MAPPER database: a multi-genome catalog of putative transcription factor binding sites.
V. D. Marinescu, I. S. Kohane, and A. Riva (2005)
Nucleic Acids Res. 33, D91-D97
   Abstract »    Full Text »    PDF »
Systems Biology and New Technologies Enable Predictive and Preventative Medicine.
L. Hood, J. R. Heath, M. E. Phelps, and B. Lin (2004)
Science 306, 640-643
   Abstract »    Full Text »    PDF »
Environmental genomics: a key to understanding biology, pathophysiology and disease.
D. A. Schwartz, J. H. Freedman, and E. A. Linney (2004)
Hum. Mol. Genet. 13, R217-R224
   Abstract »    Full Text »    PDF »
Gene expression profiles of transcription factors and signaling molecules in the ascidian embryo: towards a comprehensive understanding of gene networks.
K. S. Imai, K. Hino, K. Yagi, N. Satoh, and Y. Satou (2004)
Development 131, 4047-4058
   Abstract »    Full Text »    PDF »
Analysis of Transcription Factor Expression during Discrete Stages of Postnatal Thymocyte Differentiation.
S. Tabrizifard, A. Olaru, J. Plotkin, M. Fallahi-Sichani, F. Livak, and H. T. Petrie (2004)
J. Immunol. 173, 1094-1102
   Abstract »    Full Text »    PDF »
Identification of sparsely distributed clusters of cis-regulatory elements in sets of co-expressed genes.
G. Kreiman (2004)
Nucleic Acids Res. 32, 2889-2900
   Abstract »    Full Text »    PDF »
Err{alpha} and Gabpa/b specify PGC-1{alpha}-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle.
V. K. Mootha, C. Handschin, D. Arlow, X. Xie, J. St. Pierre, S. Sihag, W. Yang, D. Altshuler, P. Puigserver, N. Patterson, et al. (2004)
PNAS 101, 6570-6575
   Abstract »    Full Text »    PDF »
Two Functionally Identical Modular Enhancers in Drosophila Troponin T Gene Establish the Correct Protein Levels in Different Muscle Types.
J.-A. Mas, E. Garcia-Zaragoza, and M. Cervera (2004)
Mol. Biol. Cell 15, 1931-1945
   Abstract »    Full Text »    PDF »
Superfamilies of Evolved and Designed Networks.
R. Milo, S. Itzkovitz, N. Kashtan, R. Levitt, S. Shen-Orr, I. Ayzenshtat, M. Sheffer, and U. Alon (2004)
Science 303, 1538-1542
   Abstract »    Full Text »    PDF »
A Raf/MEK/ERK signaling pathway is required for development of the sea urchin embryo micromere lineage through phosphorylation of the transcription factor Ets.
E. Rottinger, L. Besnardeau, and T. Lepage (2004)
Development 131, 1075-1087
   Abstract »    Full Text »    PDF »
On Systems Thinking, Systems Biology, and the in Silico Plant.
G. L. Hammer, T. R