Global regulatory logic for specification of an embryonic cell lineage
Open accessAbstract
Explanation of a process of development must ultimately be couched in the terms of the genomic regulatory code. Specification of an embryonic cell lineage is driven by a network of interactions among genes encoding transcription factors. Here, we present the gene regulatory network (GRN) that directs the specification of the skeletogenic micromere lineage of the sea urchin embryo. The GRN now includes all regulatory genes expressed in this lineage up to late blastula stage, as identified in a genomewide survey. The architecture of the GRN was established by a large-scale perturbation analysis in which the expression of each gene in the GRN was cut off by use of morpholinos, and the effects on all other genes were measured quantitatively. Several cis -regulatory analyses provided additional evidence. The explanatory power of the GRN suffices to provide a causal explanation for all observable developmental functions of the micromere lineage during the specification period. These functions are: ( i ) initial acquisition of identity through transcriptional interpretation of localized maternal cues; ( ii ) activation of specific regulatory genes by use of a double negative gate; ( iii ) dynamic stabilization of the regulatory state by activation of a feedback subcircuit; ( iv ) exclusion of alternative regulatory states; ( v ) presentation of a signal required by the micromeres themselves and of two different signals required for development of adjacent endomesodermal lineages; and ( vi ) lineage-specific activation of batteries of skeletogenic genes. The GRN precisely predicts gene expression responses and provides a coherent explanation of the biology of specification.
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In sea urchins, a Class-specific evolutionary modification caused the acquisition of an embryonic skeleton not present in other echinoderms.
“One example of a subcircuit-level co-option event has been discovered in sea urchins, in which a Class-specific evolutionary modification has caused the acquisition of an embryonic skeleton not present in other echinoderms.”
From Evolution of Gene Regulatory Networks Controlling Body Plan Development (2011) · cites this paper as Oliveri et al., 2008
The paper describes the skeletogenic micromere lineage in modern sea urchins (Introduction, p. 1), and the Results (p. 2) show a late gastrula with a forming skeleton. It does not establish that a class-specific evolutionary modification or subcircuit co-option caused the skeleton’s acquisition, or compare its presence with other echinoderms. (LLM, conf=0.84)
Experimental — accuracy not yet measuredA comparison of regulatory gene expression in embryonic and adult skeletogenic precursor cells revealed a large overlap at least at the nodes of these GRNs, which very likely extends also to the linkages between them.
“A comparison of regulatory gene expression in embryonic and adult skeletogenic precursor cells revealed a large overlap at least at the nodes of these GRNs which very likely extends also to the linkages between them (Gao and Davidson, 2008; Oliveri et al., 2008).”
From Evolution of Gene Regulatory Networks Controlling Body Plan Development (2011) · cites this paper as Oliveri et al., 2008
The introduction (p. 1) describes a GRN for embryonic skeletogenic micromeres and says the study does not include processes after gastrulation. The Results (pp. 4–6) describe regulatory genes and linkages in that embryonic lineage, but the passages found do not compare embryonic and adult precursor cells or assess overlap in their GRN nodes or linkages. (LLM, conf=0.76)
Experimental — accuracy not yet measuredThe gene regulatory network underlying the specification and differentiation of the micromere lineage is known.
“The gene regulatory network (GRN) underlying the specification and differentiation of this lineage is now known.”
From Transfer of a large gene regulatory apparatus to a new developmental address in echinoid evolution (2008) · cites this paper as [12]
GRNs are composed of multiple sub-circuits, each accomplishing a parsed regulatory task.
“GRNs are composed of multiple sub-circuits, that is, the individual regulatory tasks into which a process can be parsed are each accomplished by a given GRN sub-circuit1–4.”
From Emerging properties of animal gene regulatory networks (2010) · cites this paper as [1]
The sea urchin skeletogenic lineage GRN portion contains 24 regulatory genes and several signalling genes, plus downstream differentiation genes.
“This portion of the network contains 24 regulatory genes and several signalling genes, as well as a sampling of downstream differentiation genes”
From Emerging properties of animal gene regulatory networks (2010) · cites this paper as [1]
The sea urchin mesoderm, endoderm, and oral/aboral ectoderm specification GRNs are deep, layered, and hierarchical.
“The GRNs underlying specification of the mesoderm, endoderm1,2,8 and of the oral and aboral ectoderm9 of the sea urchin embryo are similarly deep, layered and hierarchical.”
From Emerging properties of animal gene regulatory networks (2010) · cites this paper as [1]
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Self-citation
- Authors
- Oliveri, P., Tu, Q., & Davidson, E. H.
- Affiliations
- California Institute of Technology (US)
- Corresponding author
- Oliveri, Paola
- Davidson, Eric H.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-04-22
- Volume
- 105
- Issue
- 16
- Pages
- 5955-5962
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2329687
- OpenAlex
- W2032074345
- Cited by
- 381
- References
- 47
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 16 · 2023: 15 · 2022: 15 · 2021: 35 · 2020: 13 · 2019: 21 · 2018: 15 · 2017: 19 · 2016: 24 · 2015: 21 · 2014: 24 · 2013: 16 · 2012: 26
- FWCI
- 14.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- UCL Discovery (University College London) (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 (P01-HD037105, 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 › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- gene regulatory networks, sea urchin embryo, transcription factors, feedback loops, endomesoderm, developmental gene expression
- MeSH terms
- Animals, Skeleton, Genome, Gene Expression Regulation, Developmental, Cell Lineage, Strongylocentrotus purpuratus, Gene Regulatory Networks
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