A Wnt oscillator model for somitogenesis

Peter B Jensen; Lykke Pedersen; Sandeep Krishna; Mogens H Jensen

doi:10.1016/j.bpj.2009.11.039

A Wnt oscillator model for somitogenesis

Peter B Jensen, Lykke Pedersen, Sandeep Krishna, Mogens H Jensen

32 Citationer (Scopus)

Abstract

We propose a model for the segmentation clock in vertebrate somitogenesis, based on the Wnt signaling pathway. The core of the model is a negative feedback loop centered around the Axin2 protein. Axin2 is activated by β-catenin, which in turn is degraded by a complex of GSK3β and Axin2. The model produces oscillatory states of the involved constituents with typical time periods of a few hours (ultradian oscillations). The oscillations are robust to changes in parameter values and are often spiky, where low concentration values of β-catenin are interrupted by sharp peaks. Necessary for the oscillations is the saturated degradation of Axin2. Somite formation in chick and mouse embryos is controlled by a spatial Wnt gradient which we introduce in the model through a time-dependent decrease in Wnt3a ligand level. We find that the oscillations disappear as the ligand concentration decreases, in agreement with observations on embryos.

Originalsprog	Engelsk
Tidsskrift	Biophysical Journal
Vol/bind	98
Udgave nummer	6
Sider (fra-til)	943-950
Antal sider	8
ISSN	0006-3495
DOI	https://doi.org/10.1016/j.bpj.2009.11.039
Status	Udgivet - 17 mar. 2010

Adgang til dokumentet

10.1016/j.bpj.2009.11.039

Citationsformater

@article{0af626c0fc2e4ff8b75b5cab57a79599,

title = "A Wnt oscillator model for somitogenesis",

abstract = "We propose a model for the segmentation clock in vertebrate somitogenesis, based on the Wnt signaling pathway. The core of the model is a negative feedback loop centered around the Axin2 protein. Axin2 is activated by β-catenin, which in turn is degraded by a complex of GSK3β and Axin2. The model produces oscillatory states of the involved constituents with typical time periods of a few hours (ultradian oscillations). The oscillations are robust to changes in parameter values and are often spiky, where low concentration values of β-catenin are interrupted by sharp peaks. Necessary for the oscillations is the saturated degradation of Axin2. Somite formation in chick and mouse embryos is controlled by a spatial Wnt gradient which we introduce in the model through a time-dependent decrease in Wnt3a ligand level. We find that the oscillations disappear as the ligand concentration decreases, in agreement with observations on embryos.",

keywords = "Animals, Biological Clocks, Computer Simulation, Embryonic Development, Humans, Models, Biological, Somites, Wnt Proteins",

author = "Jensen, {Peter B} and Lykke Pedersen and Sandeep Krishna and Jensen, {Mogens H}",

year = "2010",

month = mar,

day = "17",

doi = "10.1016/j.bpj.2009.11.039",

language = "English",

volume = "98",

pages = "943--950",

journal = "Biophysical Journal",

issn = "0006-3495",

publisher = "Cell Press",

number = "6",

}

TY - JOUR

T1 - A Wnt oscillator model for somitogenesis

AU - Jensen, Peter B

AU - Pedersen, Lykke

AU - Krishna, Sandeep

AU - Jensen, Mogens H

PY - 2010/3/17

Y1 - 2010/3/17

N2 - We propose a model for the segmentation clock in vertebrate somitogenesis, based on the Wnt signaling pathway. The core of the model is a negative feedback loop centered around the Axin2 protein. Axin2 is activated by β-catenin, which in turn is degraded by a complex of GSK3β and Axin2. The model produces oscillatory states of the involved constituents with typical time periods of a few hours (ultradian oscillations). The oscillations are robust to changes in parameter values and are often spiky, where low concentration values of β-catenin are interrupted by sharp peaks. Necessary for the oscillations is the saturated degradation of Axin2. Somite formation in chick and mouse embryos is controlled by a spatial Wnt gradient which we introduce in the model through a time-dependent decrease in Wnt3a ligand level. We find that the oscillations disappear as the ligand concentration decreases, in agreement with observations on embryos.

AB - We propose a model for the segmentation clock in vertebrate somitogenesis, based on the Wnt signaling pathway. The core of the model is a negative feedback loop centered around the Axin2 protein. Axin2 is activated by β-catenin, which in turn is degraded by a complex of GSK3β and Axin2. The model produces oscillatory states of the involved constituents with typical time periods of a few hours (ultradian oscillations). The oscillations are robust to changes in parameter values and are often spiky, where low concentration values of β-catenin are interrupted by sharp peaks. Necessary for the oscillations is the saturated degradation of Axin2. Somite formation in chick and mouse embryos is controlled by a spatial Wnt gradient which we introduce in the model through a time-dependent decrease in Wnt3a ligand level. We find that the oscillations disappear as the ligand concentration decreases, in agreement with observations on embryos.

KW - Animals

KW - Biological Clocks

KW - Computer Simulation

KW - Embryonic Development

KW - Humans

KW - Models, Biological

KW - Somites

KW - Wnt Proteins

U2 - 10.1016/j.bpj.2009.11.039

DO - 10.1016/j.bpj.2009.11.039

M3 - Journal article

C2 - 20303851

SN - 0006-3495

VL - 98

SP - 943

EP - 950

JO - Biophysical Journal

JF - Biophysical Journal

IS - 6

ER -

A Wnt oscillator model for somitogenesis

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater