A provisional regulatory gene network for specification of endomesoderm in the sea urchin embryo

Eric H. Davidson, Jonathan P. Rast, Paola Oliveri, Andrew Ransick, Cristina Calestani, Chiou Hwa Yuh, Takuya Minokawa, Gabriele Amore, Veronica Hinman, César Arenas-Mena, Ochan Otim, Charles Brown, Carolina B. Livi, Pei Yun Lee, Roger Revilla, Maria J. Schilstra, Peter J.C. Clarke, Alistair G. Rust, Zhengjun Pan, Maria I. ArnoneLee Rowen, R. Andrew Cameron, David R. McClay, Leroy Hood, Hamid Bolouri

Research output: Contribution to journalArticle

249 Citations (Scopus)

Abstract

We present the current form of a provisional DNA sequence-based regulatory gene network that explains in outline how endomesodermal specification in the sea urchin embryo is controlled. The model of the network is in a continuous process of revision and growth as new genes are added and new experimental results become available; see http://www.its.caltech.edu/∼mirsky/endomeso.htm (End-mes Gene Network Update) for the latest version. The network contains over 40 genes at present, many newly uncovered in the course of this work, and most encoding DNA-binding transcriptional regulatory factors. The architecture of the network was approached initially by construction of a logic model that integrated the extensive experimental evidence now available on endomesoderm specification. The internal linkages between genes in the network have been determined functionally, by measurement of the effects of regulatory perturbations on the expression of all relevant genes in the network. Five kinds of perturbation have been applied: (1) use of morpholino antisense oligonucleotides targeted to many of the key regulatory genes in the network; (2) transformation of other regulatory factors into dominant repressors by construction of Engrailed repressor domain fusions; (3) ectopic expression of given regulatory factors, from genetic expression constructs and from injected mRNAs; (4) blockade of the β-catenin/Tcf pathway by introduction of mRNA encoding the intracellular domain of cadherin; and (5) blockade of the Notch signaling pathway by introduction of mRNA encoding the extracellular domain of the Notch receptor. The network model predicts the cis-regulatory inputs that link each gene into the network. Therefore, its architecture is testable by cis-regulatory analysis. Strongylocentrotus purpuratus and Lytechinus variegatus genomic BAC recombinants that include a large number of the genes in the network have been sequenced and annotated. Tests of the cis-regulatory predictions of the model are greatly facilitated by interspecific computational sequence comparison, which affords a rapid identification of likely cis-regulatory elements in advance of experimental analysis. The network specifies genomically encoded regulatory processes between early cleavage and gastrula stages. These control the specification of the micromere lineage and of the initial veg2 endomesodermal domain; the blastula-stage separation of the central veg2 mesodermal domain (i.e., the secondary mesenchyme progenitor field) from the peripheral veg2 endodermal domain; the stabilization of specification state within these domains; and activation of some downstream differentiation genes. Each of the temporal-spatial phases of specification is represented in a subelement of the network model, that treats regulatory events within the relevant embryonic nuclei at particular stages.

Original languageEnglish (US)
Pages (from-to)162-190
Number of pages29
JournalDevelopmental Biology
Volume246
Issue number1
DOIs
StatePublished - Jun 1 2002
Externally publishedYes

Fingerprint

Sea Urchins
Gene Regulatory Networks
Embryonic Structures
Messenger RNA
Lytechinus
Strongylocentrotus purpuratus
Genetic Complementation Test
Notch Receptors
Genes
Blastula
Gastrula
Catenins
Morpholinos
Antisense Oligonucleotides
Mesoderm
Cadherins
DNA
Growth

Keywords

  • Gene network
  • Gene regulation
  • Sea urchin embryo

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Davidson, E. H., Rast, J. P., Oliveri, P., Ransick, A., Calestani, C., Yuh, C. H., ... Bolouri, H. (2002). A provisional regulatory gene network for specification of endomesoderm in the sea urchin embryo. Developmental Biology, 246(1), 162-190. https://doi.org/10.1006/dbio.2002.0635

A provisional regulatory gene network for specification of endomesoderm in the sea urchin embryo. / Davidson, Eric H.; Rast, Jonathan P.; Oliveri, Paola; Ransick, Andrew; Calestani, Cristina; Yuh, Chiou Hwa; Minokawa, Takuya; Amore, Gabriele; Hinman, Veronica; Arenas-Mena, César; Otim, Ochan; Brown, Charles; Livi, Carolina B.; Lee, Pei Yun; Revilla, Roger; Schilstra, Maria J.; Clarke, Peter J.C.; Rust, Alistair G.; Pan, Zhengjun; Arnone, Maria I.; Rowen, Lee; Cameron, R. Andrew; McClay, David R.; Hood, Leroy; Bolouri, Hamid.

In: Developmental Biology, Vol. 246, No. 1, 01.06.2002, p. 162-190.

Research output: Contribution to journalArticle

Davidson, EH, Rast, JP, Oliveri, P, Ransick, A, Calestani, C, Yuh, CH, Minokawa, T, Amore, G, Hinman, V, Arenas-Mena, C, Otim, O, Brown, C, Livi, CB, Lee, PY, Revilla, R, Schilstra, MJ, Clarke, PJC, Rust, AG, Pan, Z, Arnone, MI, Rowen, L, Cameron, RA, McClay, DR, Hood, L & Bolouri, H 2002, 'A provisional regulatory gene network for specification of endomesoderm in the sea urchin embryo', Developmental Biology, vol. 246, no. 1, pp. 162-190. https://doi.org/10.1006/dbio.2002.0635
Davidson, Eric H. ; Rast, Jonathan P. ; Oliveri, Paola ; Ransick, Andrew ; Calestani, Cristina ; Yuh, Chiou Hwa ; Minokawa, Takuya ; Amore, Gabriele ; Hinman, Veronica ; Arenas-Mena, César ; Otim, Ochan ; Brown, Charles ; Livi, Carolina B. ; Lee, Pei Yun ; Revilla, Roger ; Schilstra, Maria J. ; Clarke, Peter J.C. ; Rust, Alistair G. ; Pan, Zhengjun ; Arnone, Maria I. ; Rowen, Lee ; Cameron, R. Andrew ; McClay, David R. ; Hood, Leroy ; Bolouri, Hamid. / A provisional regulatory gene network for specification of endomesoderm in the sea urchin embryo. In: Developmental Biology. 2002 ; Vol. 246, No. 1. pp. 162-190.
@article{79828749d9324af9b633eba742fc8375,
title = "A provisional regulatory gene network for specification of endomesoderm in the sea urchin embryo",
abstract = "We present the current form of a provisional DNA sequence-based regulatory gene network that explains in outline how endomesodermal specification in the sea urchin embryo is controlled. The model of the network is in a continuous process of revision and growth as new genes are added and new experimental results become available; see http://www.its.caltech.edu/∼mirsky/endomeso.htm (End-mes Gene Network Update) for the latest version. The network contains over 40 genes at present, many newly uncovered in the course of this work, and most encoding DNA-binding transcriptional regulatory factors. The architecture of the network was approached initially by construction of a logic model that integrated the extensive experimental evidence now available on endomesoderm specification. The internal linkages between genes in the network have been determined functionally, by measurement of the effects of regulatory perturbations on the expression of all relevant genes in the network. Five kinds of perturbation have been applied: (1) use of morpholino antisense oligonucleotides targeted to many of the key regulatory genes in the network; (2) transformation of other regulatory factors into dominant repressors by construction of Engrailed repressor domain fusions; (3) ectopic expression of given regulatory factors, from genetic expression constructs and from injected mRNAs; (4) blockade of the β-catenin/Tcf pathway by introduction of mRNA encoding the intracellular domain of cadherin; and (5) blockade of the Notch signaling pathway by introduction of mRNA encoding the extracellular domain of the Notch receptor. The network model predicts the cis-regulatory inputs that link each gene into the network. Therefore, its architecture is testable by cis-regulatory analysis. Strongylocentrotus purpuratus and Lytechinus variegatus genomic BAC recombinants that include a large number of the genes in the network have been sequenced and annotated. Tests of the cis-regulatory predictions of the model are greatly facilitated by interspecific computational sequence comparison, which affords a rapid identification of likely cis-regulatory elements in advance of experimental analysis. The network specifies genomically encoded regulatory processes between early cleavage and gastrula stages. These control the specification of the micromere lineage and of the initial veg2 endomesodermal domain; the blastula-stage separation of the central veg2 mesodermal domain (i.e., the secondary mesenchyme progenitor field) from the peripheral veg2 endodermal domain; the stabilization of specification state within these domains; and activation of some downstream differentiation genes. Each of the temporal-spatial phases of specification is represented in a subelement of the network model, that treats regulatory events within the relevant embryonic nuclei at particular stages.",
keywords = "Gene network, Gene regulation, Sea urchin embryo",
author = "Davidson, {Eric H.} and Rast, {Jonathan P.} and Paola Oliveri and Andrew Ransick and Cristina Calestani and Yuh, {Chiou Hwa} and Takuya Minokawa and Gabriele Amore and Veronica Hinman and C{\'e}sar Arenas-Mena and Ochan Otim and Charles Brown and Livi, {Carolina B.} and Lee, {Pei Yun} and Roger Revilla and Schilstra, {Maria J.} and Clarke, {Peter J.C.} and Rust, {Alistair G.} and Zhengjun Pan and Arnone, {Maria I.} and Lee Rowen and Cameron, {R. Andrew} and McClay, {David R.} and Leroy Hood and Hamid Bolouri",
year = "2002",
month = "6",
day = "1",
doi = "10.1006/dbio.2002.0635",
language = "English (US)",
volume = "246",
pages = "162--190",
journal = "Developmental Biology",
issn = "0012-1606",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - A provisional regulatory gene network for specification of endomesoderm in the sea urchin embryo

AU - Davidson, Eric H.

AU - Rast, Jonathan P.

AU - Oliveri, Paola

AU - Ransick, Andrew

AU - Calestani, Cristina

AU - Yuh, Chiou Hwa

AU - Minokawa, Takuya

AU - Amore, Gabriele

AU - Hinman, Veronica

AU - Arenas-Mena, César

AU - Otim, Ochan

AU - Brown, Charles

AU - Livi, Carolina B.

AU - Lee, Pei Yun

AU - Revilla, Roger

AU - Schilstra, Maria J.

AU - Clarke, Peter J.C.

AU - Rust, Alistair G.

AU - Pan, Zhengjun

AU - Arnone, Maria I.

AU - Rowen, Lee

AU - Cameron, R. Andrew

AU - McClay, David R.

AU - Hood, Leroy

AU - Bolouri, Hamid

PY - 2002/6/1

Y1 - 2002/6/1

N2 - We present the current form of a provisional DNA sequence-based regulatory gene network that explains in outline how endomesodermal specification in the sea urchin embryo is controlled. The model of the network is in a continuous process of revision and growth as new genes are added and new experimental results become available; see http://www.its.caltech.edu/∼mirsky/endomeso.htm (End-mes Gene Network Update) for the latest version. The network contains over 40 genes at present, many newly uncovered in the course of this work, and most encoding DNA-binding transcriptional regulatory factors. The architecture of the network was approached initially by construction of a logic model that integrated the extensive experimental evidence now available on endomesoderm specification. The internal linkages between genes in the network have been determined functionally, by measurement of the effects of regulatory perturbations on the expression of all relevant genes in the network. Five kinds of perturbation have been applied: (1) use of morpholino antisense oligonucleotides targeted to many of the key regulatory genes in the network; (2) transformation of other regulatory factors into dominant repressors by construction of Engrailed repressor domain fusions; (3) ectopic expression of given regulatory factors, from genetic expression constructs and from injected mRNAs; (4) blockade of the β-catenin/Tcf pathway by introduction of mRNA encoding the intracellular domain of cadherin; and (5) blockade of the Notch signaling pathway by introduction of mRNA encoding the extracellular domain of the Notch receptor. The network model predicts the cis-regulatory inputs that link each gene into the network. Therefore, its architecture is testable by cis-regulatory analysis. Strongylocentrotus purpuratus and Lytechinus variegatus genomic BAC recombinants that include a large number of the genes in the network have been sequenced and annotated. Tests of the cis-regulatory predictions of the model are greatly facilitated by interspecific computational sequence comparison, which affords a rapid identification of likely cis-regulatory elements in advance of experimental analysis. The network specifies genomically encoded regulatory processes between early cleavage and gastrula stages. These control the specification of the micromere lineage and of the initial veg2 endomesodermal domain; the blastula-stage separation of the central veg2 mesodermal domain (i.e., the secondary mesenchyme progenitor field) from the peripheral veg2 endodermal domain; the stabilization of specification state within these domains; and activation of some downstream differentiation genes. Each of the temporal-spatial phases of specification is represented in a subelement of the network model, that treats regulatory events within the relevant embryonic nuclei at particular stages.

AB - We present the current form of a provisional DNA sequence-based regulatory gene network that explains in outline how endomesodermal specification in the sea urchin embryo is controlled. The model of the network is in a continuous process of revision and growth as new genes are added and new experimental results become available; see http://www.its.caltech.edu/∼mirsky/endomeso.htm (End-mes Gene Network Update) for the latest version. The network contains over 40 genes at present, many newly uncovered in the course of this work, and most encoding DNA-binding transcriptional regulatory factors. The architecture of the network was approached initially by construction of a logic model that integrated the extensive experimental evidence now available on endomesoderm specification. The internal linkages between genes in the network have been determined functionally, by measurement of the effects of regulatory perturbations on the expression of all relevant genes in the network. Five kinds of perturbation have been applied: (1) use of morpholino antisense oligonucleotides targeted to many of the key regulatory genes in the network; (2) transformation of other regulatory factors into dominant repressors by construction of Engrailed repressor domain fusions; (3) ectopic expression of given regulatory factors, from genetic expression constructs and from injected mRNAs; (4) blockade of the β-catenin/Tcf pathway by introduction of mRNA encoding the intracellular domain of cadherin; and (5) blockade of the Notch signaling pathway by introduction of mRNA encoding the extracellular domain of the Notch receptor. The network model predicts the cis-regulatory inputs that link each gene into the network. Therefore, its architecture is testable by cis-regulatory analysis. Strongylocentrotus purpuratus and Lytechinus variegatus genomic BAC recombinants that include a large number of the genes in the network have been sequenced and annotated. Tests of the cis-regulatory predictions of the model are greatly facilitated by interspecific computational sequence comparison, which affords a rapid identification of likely cis-regulatory elements in advance of experimental analysis. The network specifies genomically encoded regulatory processes between early cleavage and gastrula stages. These control the specification of the micromere lineage and of the initial veg2 endomesodermal domain; the blastula-stage separation of the central veg2 mesodermal domain (i.e., the secondary mesenchyme progenitor field) from the peripheral veg2 endodermal domain; the stabilization of specification state within these domains; and activation of some downstream differentiation genes. Each of the temporal-spatial phases of specification is represented in a subelement of the network model, that treats regulatory events within the relevant embryonic nuclei at particular stages.

KW - Gene network

KW - Gene regulation

KW - Sea urchin embryo

UR - http://www.scopus.com/inward/record.url?scp=0036607698&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036607698&partnerID=8YFLogxK

U2 - 10.1006/dbio.2002.0635

DO - 10.1006/dbio.2002.0635

M3 - Article

C2 - 12027441

AN - SCOPUS:0036607698

VL - 246

SP - 162

EP - 190

JO - Developmental Biology

JF - Developmental Biology

SN - 0012-1606

IS - 1

ER -