An otx cis -regulatory module: a key node in the sea urchin endomesoderm gene regulatory network
Open accessAbstract
An essential node in the gene regulatory network (GRN) for endomesoderm specification in the sea urchin embryo lies within the regulatory system of the otx gene. According to the predictions of the GRN, based on perturbation analysis and expression data, the beta1/2 transcription unit of this gene is engaged during specification in interactions with two other regulatory genes, krox and gatae. It is predicted to be driven into activity by the krox gene, to form a positively reinforcing functional loop with the gatae gene, and to respond to its own output as well. Here we isolate the relevant otx cis-regulatory element, and examine the specific input predictions of the GRN at the level of its genomic DNA sequence. This beta1/2-otx regulatory module performs the necessary functions, as shown by use of expression constructs. It requires gatae, otx, and krox inputs, as predicted, and it operates as an "AND" logic processor in that removal of any one of these inputs essentially destroys activity. The necessary target sites were identified in the module sequence, and mutation of these sites was demonstrated to produce the same respective effects on construct expression as does blocking its regulatory inputs by treatment with morpholino antisense oligonucleotides. For spatial expression in the endoderm, one particular pair of Gata sites is essential and these function synergistically with an adjacent Otx site. We thus demonstrate directly the structure/function relationships of the genomic regulatory code, at this key node of the endomesoderm GRN.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
There is a compensatory cis-regulatory change upstream of the kernel, in the substitution of blimp1 in the sea urchin for tbr as an early cis-regulatory input initiating otx expression.
“In addition, there is a compensatory cis -regulatory change upstream of the kernel, in the substitution of blimp1 in the sea urchin for tbr as an early cis -regulatory input initiating otx expression (29, 30).”
From Evolutionary plasticity of developmental gene regulatory network architecture (2007) · cites this paper as [30]
Cites
A genomic regulatory network for development
Davidson, E. H., Rast, J. P., Oliveri, P., Ransick, A., Calestani, C., Yuh, C.-H., Minokawa, T., Amore, G., Hinman, V., Arenas-Mena, C., et al. (2002) · Science · doi:10.1126/science.1069883 · Cited by 1,567 · see citing works
Self-citationGenomic Regulatory Systems: Development and Evolution
Davidson, E. H. (2005) · Thammasat University Digital Collections · Cited by 690 · see citing works
Self-citationGenomic Cis-Regulatory Logic: Experimental and Computational Analysis of a Sea Urchin Gene
Yuh, C., Bolouri, H., & Davidson, E. H. (1998) · Science · doi:10.1126/science.279.5358.1896 · Cited by 682 · see citing works
Self-citationThe bicoid protein is a positive regulator of hunchback transcription in the early Drosophila embryo
Driever, W., & Nüsslein‐Volhard, C. (1989) · Nature · doi:10.1038/337138a0 · Cited by 663 · see citing works
Nuclear β-catenin is required to specify vegetal cell fates in the sea urchin embryo
Logan, C. Y., Miller, J. R., Ferkowicz, M. J., & McClay, D. R. (1999) · Development · doi:10.1242/dev.126.2.345 · Cited by 456 · see citing works
Lowry, J. A., & Atchley, W. R. (2000) · Journal of Molecular Evolution · doi:10.1007/s002399910012 · Cited by 359 · see citing works
A Provisional Regulatory Gene Network for Specification of Endomesoderm in the Sea Urchin Embryo
Davidson, E. H., Rast, J. P., Oliveri, P., Ransick, A., Calestani, C., Yuh, C., Minokawa, T., Amore, G., Hinman, V. F., Arenas‐Mena, C., et al. (2002) · Developmental Biology · doi:10.1006/dbio.2002.0635 · Cited by 338 · see citing works
Self-citationWikramanayake, A. H., Huang, L., & Klein, W. H. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.16.9343 · Cited by 287 · see citing works
Developmental gene regulatory network architecture across 500 million years of echinoderm evolution
Hinman, V. F., Nguyen, A. T., Cameron, R. A., & Davidson, E. H. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2235868100 · Cited by 272 · see citing works
Self-citationA Regulatory Gene Network That Directs Micromere Specification in the Sea Urchin Embryo
Oliveri, P., Carrick, D. M., & Davidson, E. H. (2002) · Developmental Biology · doi:10.1006/dbio.2002.0627 · Cited by 251 · see citing works
Self-citationRegulatory gene networks and the properties of the developmental process
Davidson, E. H., McClay, D. R., & Hood, L. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0437746100 · Cited by 238 · see citing works
Self-citationMcMahon, A. P., Flytzanis, C. N., Hough‐Evans, B. R., et al. (1985) · Developmental Biology · doi:10.1016/0012-1606(85)90045-4 · Cited by 227 · see citing works
Ransick, A., Rast, J. P., Minokawa, T., Calestani, C., & Davidson, E. H. (2002) · Developmental Biology · doi:10.1006/dbio.2002.0607 · Cited by 152 · see citing works
Self-citationModular cis-regulatory organization of Endo16, a gut-specific gene of the sea urchin embryo
Yuh, C., & Davidson, E. H. (1996) · Development · doi:10.1242/dev.122.4.1069 · Cited by 141 · see citing works
Self-citationRansick, A., Ernst, S. G., Britten, R. J., & Davidson, E. H. (1993) · Mechanisms of Development · doi:10.1016/0925-4773(93)90001-e · Cited by 128 · see citing works
Self-citationCalzone, F. J., Thézé, N., Thiébaud, P., Hill, R. L., Britten, R. J., & Davidson, E. H. (1988) · Genes & Development · doi:10.1101/gad.2.9.1074 · Cited by 112 · see citing works
Self-citationNew Computational Approaches for Analysis of cis-Regulatory Networks
Brown, C. T., Rust, A. G., Clarke, P., Pan, Z., Schilstra, M. J., Buysscher, T. D., Griffin, G. J., Wold, B. J., Cameron, R. A., Davidson, E. H., et al. (2002) · Developmental Biology · doi:10.1006/dbio.2002.0619 · Cited by 110 · see citing works
Self-citationAngerer, L. M., Oleksyn, D. W., Levine, A. M., Li, X., Klein, W. H., & Angerer, R. C. (2001) · Development · doi:10.1242/dev.128.22.4393 · Cited by 107 · see citing works
Kirchhamer, C. V., Yuh, C., & Davidson, E. H. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.18.9322 · Cited by 105 · see citing works
Self-citationYuh, C., Brown, C. T., Livi, C. B., Rowen, L., Clarke, P. J. C., & Davidson, E. H. (2002) · Developmental Biology · doi:10.1006/dbio.2002.0618 · Cited by 102 · see citing works
Self-citationModeling DNA Sequence-Based cis-Regulatory Gene Networks
Bolouri, H., & Davidson, E. H. (2002) · Developmental Biology · doi:10.1006/dbio.2002.0617 · Cited by 82 · see citing works
Self-citationInducible expression of a cloned heat shock fusion gene in sea urchin embryos.
McMahon, A. P., Novak, T. J., Britten, R. J., et al. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.23.7490 · Cited by 80 · see citing works
Chapter 1 Laboratory Culture of Strongylocentrotus purpuratus Adults, Embryos, and Larvae
Leahy, P. S. (1986) · Methods in cell biology · doi:10.1016/s0091-679x(08)60339-8 · Cited by 78 · see citing works
Li, X., Chuang, C.-K., Mao, C., Angerer, L. M., & Klein, W. H. (1997) · Developmental Biology · doi:10.1006/dbio.1997.8610 · Cited by 70 · see citing works
Review: The Role of IRF-4 in Transcriptional Regulation
Marecki, S., & Fenton, M. J. (2002) · Journal of Interferon & Cytokine Research · doi:10.1089/107999002753452737 · Cited by 67 · see citing works
Multiple Otx Binding Sites Required for Expression of the Strongylocentrotus purpuratus Spec2a Gene
Mao, C., Gan, L., & Klein, W. H. (1994) · Developmental Biology · doi:10.1006/dbio.1994.1249 · Cited by 62 · see citing works
Tunyaplin, C. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.24.4846 · Cited by 54 · see citing works
Stage-Specific Modulation of IFN-Regulatory Factor 4 Function by Kruppel-Type Zinc Finger Proteins
Gupta, S. K., Anthony, A., & Pernis, A. B. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.10.6104 · Cited by 49 · see citing works
Li, X., Wikramanayake, A. H., & Klein, W. H. (1999) · Developmental Biology · doi:10.1006/dbio.1999.9360 · Cited by 48 · see citing works
Wang, W., Wikramanayake, A. H., Gonzalez-Rimbau, M. F., Vlahou, A., Flytzanis, C. N., & Klein, W. H. (1996) · Mechanisms of Development · doi:10.1016/s0925-4773(96)00614-4 · Cited by 41 · see citing works
Direct introduction of cloned DNA into the sea urchin zygote nucleus, and fate of injected DNA
Franks, R. R., Hough‐Evans, B. R., Britten, R. J., & Davidson, E. H. (1988) · Development · doi:10.1242/dev.102.2.287 · Cited by 41 · see citing works
Self-citationYuh, C., Li, X., Davidson, E. H., et al. (2001) · Developmental Biology · doi:10.1006/dbio.2001.0207 · Cited by 34 · see citing works
Self-citationGan, L., & Klein, W. H. (1993) · Developmental Biology · doi:10.1006/dbio.1993.1117 · Cited by 25 · see citing works
Activin-like signal activates dorsal-specific maternal RNA between 8- and 16-cell stages ofXenopus
Hainski, A. M., & Moody, S. A. (1996) · Developmental Genetics · doi:10.1002/(sici)1520-6408(1996)19:3 · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The endoderm gene regulatory network in sea urchin embryos up to mid-blastula stage
Peter, I. S., & Davidson, E. H. (2010) · Developmental Biology · doi:10.1016/j.ydbio.2009.10.037 · Cited by 150 · see citing works
Self-citationRepression of mesodermal fate by<i>foxa</i>, a key endoderm regulator of the sea urchin embryo
Oliveri, P., Walton, K. D., Davidson, E. H., & McClay, D. R. (2006) · Development · doi:10.1242/dev.02577 · Cited by 141 · see citing works
Self-citationEvolutionary plasticity of developmental gene regulatory network architecture
Hinman, V. F., & Davidson, E. H. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709994104 · Cited by 154 · see citing works
Self-citationSmith, J., & Davidson, E. H. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806442105 · Cited by 69 · see citing works
Self-citationHinman, V. F., Nguyen, A., & Davidson, E. H. (2007) · Developmental Biology · doi:10.1016/j.ydbio.2007.09.006 · Cited by 67 · see citing works
Self-citation
- Authors
- Yuh, C.-H., Dorman, E. R., Howard, M. L., & Davidson, E. H.
- Affiliations
- California Institute of Technology (US)
- Corresponding author
- Davidson, Eric H
- ORCID
- Yuh, Chiou-Hwa
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2004-05
- Volume
- 269
- Issue
- 2
- Pages
- 536-551
- ISSN
- 0012-1606 (ISSN-L)
- OpenAlex
- W2017132951
- Cited by
- 75
- References
- 34
- Citations by year
- 2025: 4 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 2 · 2014: 1 · 2013: 1 · 2012: 6
- FWCI
- 3.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Funders
- National Institutes of Health (5p01hd037105-20)
- National Institute of General Medical Sciences (GM 61005, R01GM061005)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD37105)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- cis-regulatory modules, endomesoderm specification, gene regulatory networks, sea urchin embryo, transcription factor binding sites, morpholino antisense oligonucleotides, structure-function relationship
- MeSH terms
- Animals, Endoderm, Mesoderm, Sea Urchins, Homeodomain Proteins, Gene Expression Regulation, Developmental, Otx Transcription Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
