Intrinsic noise, Delta-Notch signalling and delayed reactions promote sustained, coherent, synchronized oscillations in the presomitic mesoderm

Using a stochastic individual-based modelling approach, we examine the role that Delta-Notch signalling plays in the regulation of a robust and reliable somite segmentation clock. We find that not only can Delta-Notch signalling synchronize noisy cycles of gene expression in adjacent cells in the presomitic mesoderm (as is known), but it can also amplify and increase the coherence of these cycles. We examine some of the shortcomings of deterministic approaches to modelling these cycles and demonstrate how intrinsic noise can play an active role in promoting sustained oscillations, giving rise to noise-induced quasi-cycles. Finally, we explore how translational/transcriptional delays can result in the cycles in neighbouring cells oscillating in anti-phase and we study how this effect relates to the propagation of noise-induced stochastic waves.

Download Full-text

Faculty Opinions recommendation of Receptor tyrosine phosphatase psi is required for Delta/Notch signalling and cyclic gene expression in the presomitic mesoderm.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1020702.237451 ◽

2004 ◽

Author(s):

Judith S Eisen

Keyword(s):

Gene Expression ◽

Tyrosine Phosphatase ◽

Notch Signalling ◽

Presomitic Mesoderm ◽

Cyclic Gene ◽

Receptor Tyrosine Phosphatase

Download Full-text

Cellular Synchronisation through Unidirectional and Phase-Gated Signalling

10.1101/2020.11.26.399683 ◽

2020 ◽

Author(s):

Gregory Roth ◽

Georgios Misailidis ◽

Charisios D. Tsiairis

Keyword(s):

Gene Expression ◽

Notch Signalling ◽

The Other ◽

Cell Populations ◽

Coupling Mechanism ◽

Presomitic Mesoderm ◽

Unidirectional Coupling ◽

Alternative Framework ◽

Oscillatory Dynamics

AbstractMultiple natural and artificial oscillator systems achieve synchronisation when oscillators are coupled. The coupling mechanism, essentially the communication between oscillators, is often assumed to be continuous and bidirectional. However, the cells of the presomitic mesoderm synchronise their gene expression oscillations through Notch signalling, which is intermittent and directed from a ligand-presenting to a receptor-presenting cell. Motivated by this mode of communication we present a phase-gated and unidirectional coupling mechanism. We identify conditions under which it can successfully bring two or more oscillators to cycle in-phase. In the presomitic mesoderm we observed the oscillatory dynamics of two synchronizing cell populations and record one population halting its pace while the other keeps undisturbed, as would be predicted from our model. For the same system another important prediction, convergence to a specific range of phases upon synchronisation is also confirmed. Thus, the proposed mechanism accurately describes the coordinated oscillations of the presomitic mesoderm cells and provides an alternative framework for deciphering synchronisation.

Download Full-text

her1, a zebrafish pair-rule like gene, acts downstream of notch signalling to control somite development

Development ◽

10.1242/dev.126.13.3005 ◽

1999 ◽

Vol 126 (13) ◽

pp. 3005-3014 ◽

Cited By ~ 8

Author(s):

C. Takke ◽

J.A. Campos-Ortega

Keyword(s):

Active Form ◽

Notch Signalling ◽

Paraxial Mesoderm ◽

Presomitic Mesoderm ◽

Essentially Normal ◽

Early Embryos ◽

Somite Formation ◽

Genes Encoding ◽

Ectopic Activation ◽

Pair Rule

During vertebrate embryonic development, the paraxial mesoderm becomes subdivided into metameric units known as somites. In the zebrafish embryo, genes encoding homologues of the proteins of the Drosophila Notch signalling pathway are expressed in the presomitic mesoderm and expression is maintained in a segmental pattern during somitogenesis. This expression pattern suggests a role for these genes during somite development. We misexpressed various zebrafish genes of this group by injecting mRNA into early embryos. RNA encoding a constitutively active form of notch1a (notch1a-intra) and a truncated variant of deltaD [deltaD(Pst)], as well as transcripts of deltaC and deltaD, the hairy-E(spl) homologues her1 and her4, and groucho2 were tested for their effects on somite formation, myogenesis and on the pattern of transcription of putative downstream genes. In embryos injected with any of these RNAs, with the exception of groucho2 RNA, the paraxial mesoderm differentiated normally into somitic tissue, but failed to segment correctly. Activation of notch results in ectopic activation of her1 and her4. This misregulation of the expression of her genes might be causally related to the observed mesodermal defects, as her1 and her4 mRNA injections led to effects similar to those seen with notch1a-intra. deltaC and deltaD seem to function after subdivision of the presomitic mesoderm, since the her gene transcription pattern in the presomitic mesoderm remains essentially normal after misexpression of delta genes. Whereas notch signalling alone apparently does not affect myogenesis, zebrafish groucho2 is involved in differentiation of mesodermal derivatives.

Download Full-text

Modeling of segmentation clock mechanism in presomitic mesoderm

10.1109/iembs.2009.5333510 ◽

2009 ◽

Cited By ~ 1

Author(s):

A. Kazama ◽

A. Karashima ◽

N. Katayama ◽

M. Nakao

Keyword(s):

Presomitic Mesoderm ◽

Segmentation Clock ◽

Clock Mechanism

Download Full-text

Sustained oscillations and time delays in gene expression of protein Hes1

FEBS Letters ◽

10.1016/s0014-5793(03)00279-5 ◽

2003 ◽

Vol 541 (1-3) ◽

pp. 176-177 ◽

Cited By ~ 107

Author(s):

M.H Jensen ◽

K Sneppen ◽

G Tiana

Keyword(s):

Gene Expression ◽

Time Delays ◽

Sustained Oscillations

Download Full-text

A Nomenclature for Prospective Somites and Phases of Cyclic Gene Expression in the Presomitic Mesoderm

Developmental Cell ◽

10.1016/s1534-5807(01)00082-x ◽

2001 ◽

Vol 1 (5) ◽

pp. 619-620 ◽

Cited By ~ 71

Author(s):

Olivier Pourquié ◽

Patrick P.L. Tam

Keyword(s):

Gene Expression ◽

Presomitic Mesoderm ◽

Cyclic Gene

Download Full-text

Buffering gene expression noise by microRNA based feedforward regulation

10.1101/310656 ◽

2018 ◽

Cited By ~ 2

Author(s):

Pavol Bokes ◽

Michal Hojcka ◽

Abhyudai Singh

Keyword(s):

Gene Expression ◽

Large Scale ◽

Optimal Parameter ◽

Kinetic Monte Carlo ◽

Reaction Network ◽

Fano Factor ◽

Intrinsic Noise ◽

Limit Function ◽

Gene Expression Noise ◽

Expression Noise

AbstractCells use various regulatory motifs, including feedforward loops, to control the intrinsic noise that arises in gene expression at low copy numbers. Here we study one such system, which is broadly inspired by the interaction between an mRNA molecule and an antagonistic microRNA molecule encoded by the same gene. The two reaction species are synchronously produced, individually degraded, and the second species (microRNA) exerts an antagonistic pressure on the first species (mRNA). Using linear-noise approximation, we show that the noise in the first species, which we quantify by the Fano factor, is sub-Poissonian, and exhibits a nonmonotonic response both to the species lifetime ratio and to the strength of the antagonistic interaction. Additionally, we use the Chemical Reaction Network Theory to prove that the first species distribution is Poissonian if the first species is much more stable than the second. Finally, we identify a special parametric regime, supporting a broad range of behaviour, in which the distribution can be analytically described in terms of the confluent hypergeometric limit function. We verify our analysis against large-scale kinetic Monte Carlo simulations. Our results indicate that, subject to specific physiological constraints, optimal parameter values can be found within the mRNA-microRNA motif that can benefit the cell by lowering the gene-expression noise.

Download Full-text

Brief communication: Long-term absence of Langerhans cells alters the gene expression profile of keratinocytes and dendritic epidermal T cells

10.1101/844530 ◽

2019 ◽

Author(s):

Qingtai Su ◽

Aurélie Bouteau ◽

Jacob Cardenas ◽

Balaji Uthra ◽

Yuanyaun Wang ◽

...

Keyword(s):

Gene Expression ◽

T Cells ◽

Immune Cells ◽

Langerhans Cells ◽

Local Environment ◽

Active Role ◽

Data Interpretation ◽

Significant Gene ◽

Dendritic Epidermal T Cells

ABSTRACTTissue-resident and infiltrating immune cells are continuously exposed to molecules derived from the niche cells that often come in form of secreted factors, such as cytokines. These factors are known to impact the immune cells’ biology. However, very little is known about whether the tissue resident immune cells in return also affect the local environment. In this study, with the help of RNA-sequencing, we show for the first time that long-term absence of epidermal resident Langerhans cells (LCs) led to significant gene expression changes in the local keratinocytes and resident dendritic epidermal T cells. Thus, immune cells might play an active role in maintaining tissue homeostasis, which should be taken in consideration at data interpretation.

Download Full-text

Thylacine 1 is expressed segmentally within the paraxial mesoderm of the Xenopus embryo and interacts with the Notch pathway

Development ◽

10.1242/dev.125.11.2041 ◽

1998 ◽

Vol 125 (11) ◽

pp. 2041-2051 ◽

Cited By ~ 4

Author(s):

D.B. Sparrow ◽

W.C. Jen ◽

S. Kotecha ◽

N. Towers ◽

C. Kintner ◽

...

Keyword(s):

Expression Patterns ◽

Ectopic Expression ◽

Notch Pathway ◽

Notch Signalling ◽

Xenopus Embryo ◽

Paraxial Mesoderm ◽

Marker Genes ◽

Transcription Activator ◽

Presomitic Mesoderm ◽

Helix Loop Helix

The presomitic mesoderm of vertebrates undergoes a process of segmentation in which cell-cell interactions mediated by the Notch family of receptors and their associated ligands are involved. The vertebrate homologues of Drosophila Δ are expressed in a dynamic, segmental pattern within the presomitic mesoderm, and alterations in the function of these genes leads to a perturbed pattern of somite segmentation. In this study we have characterised Thylacine 1 which encodes a basic helix-loop-helix class transcription activator. Expression of Thylacine is restricted to the presomitic mesoderm, localising to the anterior half of several somitomeres in register with domains of X-Delta-2 expression. Ectopic expression of Thylacine in embryos causes segmentation defects similar to those seen in embryos in which Notch signalling is altered, and these embryos also show severe disruption in the expression patterns of the marker genes X-Delta-2 and X-ESR5 within the presomitic mesoderm. Finally, the expression of Thylacine is altered in embryos when Notch signalling is perturbed. These observations suggest strongly that Thylacine 1 has a role in the segmentation pathway of the Xenopus embryo, by interacting with the Notch signalling pathway.

Download Full-text