Fast synchronization of ultradian oscillators controlled by delta-notch signaling with cis-inhibition.
While it is known that a large fraction of vertebrate genes are under the control of a gene regulatory network (GRN) forming a clock with circadian periodicity, shorter period oscillatory genes like the Hairy-enhancer-of split (Hes) genes are discussed mostly in connection with the embryonic process...
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doaj-58495b9b848946f4bf683f798c11a0bb2020-11-25T01:46:02ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582014-10-011010e100384310.1371/journal.pcbi.1003843Fast synchronization of ultradian oscillators controlled by delta-notch signaling with cis-inhibition.Hendrik B TiedemannElida SchneltzerStefan ZeiserWolfgang WurstJohannes BeckersGerhard K H PrzemeckMartin Hrabě de AngelisWhile it is known that a large fraction of vertebrate genes are under the control of a gene regulatory network (GRN) forming a clock with circadian periodicity, shorter period oscillatory genes like the Hairy-enhancer-of split (Hes) genes are discussed mostly in connection with the embryonic process of somitogenesis. They form the core of the somitogenesis-clock, which orchestrates the periodic separation of somites from the presomitic mesoderm (PSM). The formation of sharp boundaries between the blocks of many cells works only when the oscillators in the cells forming the boundary are synchronized. It has been shown experimentally that Delta-Notch (D/N) signaling is responsible for this synchronization. This process has to happen rather fast as a cell experiences at most five oscillations from its 'birth' to its incorporation into a somite. Computer simulations describing synchronized oscillators with classical modes of D/N-interaction have difficulties to achieve synchronization in an appropriate time. One approach to solving this problem of modeling fast synchronization in the PSM was the consideration of cell movements. Here we show that fast synchronization of Hes-type oscillators can be achieved without cell movements by including D/N cis-inhibition, wherein the mutual interaction of DELTA and NOTCH in the same cell leads to a titration of ligand against receptor so that only one sort of molecule prevails. Consequently, the symmetry between sender and receiver is partially broken and one cell becomes preferentially sender or receiver at a given moment, which leads to faster entrainment of oscillators. Although not yet confirmed by experiment, the proposed mechanism of enhanced synchronization of mesenchymal cells in the PSM would be a new distinct developmental mechanism employing D/N cis-inhibition. Consequently, the way in which Delta-Notch signaling was modeled so far should be carefully reconsidered.http://europepmc.org/articles/PMC4196275?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hendrik B Tiedemann Elida Schneltzer Stefan Zeiser Wolfgang Wurst Johannes Beckers Gerhard K H Przemeck Martin Hrabě de Angelis |
spellingShingle |
Hendrik B Tiedemann Elida Schneltzer Stefan Zeiser Wolfgang Wurst Johannes Beckers Gerhard K H Przemeck Martin Hrabě de Angelis Fast synchronization of ultradian oscillators controlled by delta-notch signaling with cis-inhibition. PLoS Computational Biology |
author_facet |
Hendrik B Tiedemann Elida Schneltzer Stefan Zeiser Wolfgang Wurst Johannes Beckers Gerhard K H Przemeck Martin Hrabě de Angelis |
author_sort |
Hendrik B Tiedemann |
title |
Fast synchronization of ultradian oscillators controlled by delta-notch signaling with cis-inhibition. |
title_short |
Fast synchronization of ultradian oscillators controlled by delta-notch signaling with cis-inhibition. |
title_full |
Fast synchronization of ultradian oscillators controlled by delta-notch signaling with cis-inhibition. |
title_fullStr |
Fast synchronization of ultradian oscillators controlled by delta-notch signaling with cis-inhibition. |
title_full_unstemmed |
Fast synchronization of ultradian oscillators controlled by delta-notch signaling with cis-inhibition. |
title_sort |
fast synchronization of ultradian oscillators controlled by delta-notch signaling with cis-inhibition. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Computational Biology |
issn |
1553-734X 1553-7358 |
publishDate |
2014-10-01 |
description |
While it is known that a large fraction of vertebrate genes are under the control of a gene regulatory network (GRN) forming a clock with circadian periodicity, shorter period oscillatory genes like the Hairy-enhancer-of split (Hes) genes are discussed mostly in connection with the embryonic process of somitogenesis. They form the core of the somitogenesis-clock, which orchestrates the periodic separation of somites from the presomitic mesoderm (PSM). The formation of sharp boundaries between the blocks of many cells works only when the oscillators in the cells forming the boundary are synchronized. It has been shown experimentally that Delta-Notch (D/N) signaling is responsible for this synchronization. This process has to happen rather fast as a cell experiences at most five oscillations from its 'birth' to its incorporation into a somite. Computer simulations describing synchronized oscillators with classical modes of D/N-interaction have difficulties to achieve synchronization in an appropriate time. One approach to solving this problem of modeling fast synchronization in the PSM was the consideration of cell movements. Here we show that fast synchronization of Hes-type oscillators can be achieved without cell movements by including D/N cis-inhibition, wherein the mutual interaction of DELTA and NOTCH in the same cell leads to a titration of ligand against receptor so that only one sort of molecule prevails. Consequently, the symmetry between sender and receiver is partially broken and one cell becomes preferentially sender or receiver at a given moment, which leads to faster entrainment of oscillators. Although not yet confirmed by experiment, the proposed mechanism of enhanced synchronization of mesenchymal cells in the PSM would be a new distinct developmental mechanism employing D/N cis-inhibition. Consequently, the way in which Delta-Notch signaling was modeled so far should be carefully reconsidered. |
url |
http://europepmc.org/articles/PMC4196275?pdf=render |
work_keys_str_mv |
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