Setting the tempo in development: an investigation of the zebrafish somite clock mechanism.

François Giudicelli, Ertuǧrul M. Ozbudak, Gavin J. Wright, Julian Lewis

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

The somites of the vertebrate embryo are clocked out sequentially from the presomitic mesoderm (PSM) at the tail end of the embryo. Formation of each somite corresponds to one cycle of oscillation of the somite segmentation clock--a system of genes whose expression switches on and off periodically in the cells of the PSM. We have previously proposed a simple mathematical model explaining how the oscillations, in zebrafish at least, may be generated by a delayed negative feedback loop in which the products of two Notch target genes, her1 and her7, directly inhibit their own transcription, as well as that of the gene for the Notch ligand DeltaC; Notch signalling via DeltaC keeps the oscillations of neighbouring cells in synchrony. Here we subject the model to quantitative tests. We show how to read temporal information from the spatial pattern of stripes of gene expression in the anterior PSM and in this way obtain values for the biosynthetic delays and molecular lifetimes on which the model critically depends. Using transgenic lines of zebrafish expressing her1 or her7 under heat-shock control, we confirm the regulatory relationships postulated by the model. From the timing of somite segmentation disturbances following a pulse of her7 misexpression, we deduce that although her7 continues to oscillate in the anterior half of the PSM, it governs the future somite segmentation behaviour of the cells only while they are in the posterior half. In general, the findings strongly support the mathematical model of how the somite clock works, but they do not exclude the possibility that other oscillator mechanisms may operate upstream from the her7/her1 oscillator or in parallel with it.

Original languageEnglish (US)
JournalPLoS Biology
Volume5
Issue number6
DOIs
StatePublished - Jun 2007
Externally publishedYes

Fingerprint

Somites
Zebrafish
Danio rerio
oscillation
Clocks
Mesoderm
Gene expression
embryo (animal)
mathematical models
Genes
Mathematical models
gene expression
cells
Transcription
heat stress
Theoretical Models
tail
genes
Embryonic Structures
transcription (genetics)

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Setting the tempo in development : an investigation of the zebrafish somite clock mechanism. / Giudicelli, François; Ozbudak, Ertuǧrul M.; Wright, Gavin J.; Lewis, Julian.

In: PLoS Biology, Vol. 5, No. 6, 06.2007.

Research output: Contribution to journalArticle

Giudicelli, François ; Ozbudak, Ertuǧrul M. ; Wright, Gavin J. ; Lewis, Julian. / Setting the tempo in development : an investigation of the zebrafish somite clock mechanism. In: PLoS Biology. 2007 ; Vol. 5, No. 6.
@article{a1de10f774e04b189d4024556569afd7,
title = "Setting the tempo in development: an investigation of the zebrafish somite clock mechanism.",
abstract = "The somites of the vertebrate embryo are clocked out sequentially from the presomitic mesoderm (PSM) at the tail end of the embryo. Formation of each somite corresponds to one cycle of oscillation of the somite segmentation clock--a system of genes whose expression switches on and off periodically in the cells of the PSM. We have previously proposed a simple mathematical model explaining how the oscillations, in zebrafish at least, may be generated by a delayed negative feedback loop in which the products of two Notch target genes, her1 and her7, directly inhibit their own transcription, as well as that of the gene for the Notch ligand DeltaC; Notch signalling via DeltaC keeps the oscillations of neighbouring cells in synchrony. Here we subject the model to quantitative tests. We show how to read temporal information from the spatial pattern of stripes of gene expression in the anterior PSM and in this way obtain values for the biosynthetic delays and molecular lifetimes on which the model critically depends. Using transgenic lines of zebrafish expressing her1 or her7 under heat-shock control, we confirm the regulatory relationships postulated by the model. From the timing of somite segmentation disturbances following a pulse of her7 misexpression, we deduce that although her7 continues to oscillate in the anterior half of the PSM, it governs the future somite segmentation behaviour of the cells only while they are in the posterior half. In general, the findings strongly support the mathematical model of how the somite clock works, but they do not exclude the possibility that other oscillator mechanisms may operate upstream from the her7/her1 oscillator or in parallel with it.",
author = "Fran{\cc}ois Giudicelli and Ozbudak, {Ertuǧrul M.} and Wright, {Gavin J.} and Julian Lewis",
year = "2007",
month = "6",
doi = "10.1371/journal.pbio.0050150",
language = "English (US)",
volume = "5",
journal = "PLoS Biology",
issn = "1544-9173",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - Setting the tempo in development

T2 - an investigation of the zebrafish somite clock mechanism.

AU - Giudicelli, François

AU - Ozbudak, Ertuǧrul M.

AU - Wright, Gavin J.

AU - Lewis, Julian

PY - 2007/6

Y1 - 2007/6

N2 - The somites of the vertebrate embryo are clocked out sequentially from the presomitic mesoderm (PSM) at the tail end of the embryo. Formation of each somite corresponds to one cycle of oscillation of the somite segmentation clock--a system of genes whose expression switches on and off periodically in the cells of the PSM. We have previously proposed a simple mathematical model explaining how the oscillations, in zebrafish at least, may be generated by a delayed negative feedback loop in which the products of two Notch target genes, her1 and her7, directly inhibit their own transcription, as well as that of the gene for the Notch ligand DeltaC; Notch signalling via DeltaC keeps the oscillations of neighbouring cells in synchrony. Here we subject the model to quantitative tests. We show how to read temporal information from the spatial pattern of stripes of gene expression in the anterior PSM and in this way obtain values for the biosynthetic delays and molecular lifetimes on which the model critically depends. Using transgenic lines of zebrafish expressing her1 or her7 under heat-shock control, we confirm the regulatory relationships postulated by the model. From the timing of somite segmentation disturbances following a pulse of her7 misexpression, we deduce that although her7 continues to oscillate in the anterior half of the PSM, it governs the future somite segmentation behaviour of the cells only while they are in the posterior half. In general, the findings strongly support the mathematical model of how the somite clock works, but they do not exclude the possibility that other oscillator mechanisms may operate upstream from the her7/her1 oscillator or in parallel with it.

AB - The somites of the vertebrate embryo are clocked out sequentially from the presomitic mesoderm (PSM) at the tail end of the embryo. Formation of each somite corresponds to one cycle of oscillation of the somite segmentation clock--a system of genes whose expression switches on and off periodically in the cells of the PSM. We have previously proposed a simple mathematical model explaining how the oscillations, in zebrafish at least, may be generated by a delayed negative feedback loop in which the products of two Notch target genes, her1 and her7, directly inhibit their own transcription, as well as that of the gene for the Notch ligand DeltaC; Notch signalling via DeltaC keeps the oscillations of neighbouring cells in synchrony. Here we subject the model to quantitative tests. We show how to read temporal information from the spatial pattern of stripes of gene expression in the anterior PSM and in this way obtain values for the biosynthetic delays and molecular lifetimes on which the model critically depends. Using transgenic lines of zebrafish expressing her1 or her7 under heat-shock control, we confirm the regulatory relationships postulated by the model. From the timing of somite segmentation disturbances following a pulse of her7 misexpression, we deduce that although her7 continues to oscillate in the anterior half of the PSM, it governs the future somite segmentation behaviour of the cells only while they are in the posterior half. In general, the findings strongly support the mathematical model of how the somite clock works, but they do not exclude the possibility that other oscillator mechanisms may operate upstream from the her7/her1 oscillator or in parallel with it.

UR - http://www.scopus.com/inward/record.url?scp=38449107242&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38449107242&partnerID=8YFLogxK

U2 - 10.1371/journal.pbio.0050150

DO - 10.1371/journal.pbio.0050150

M3 - Article

C2 - 17535112

AN - SCOPUS:34250316233

VL - 5

JO - PLoS Biology

JF - PLoS Biology

SN - 1544-9173

IS - 6

ER -