PUBLICATION
Noise in the Vertebrate Segmentation Clock Is Boosted by Time Delays but Tamed by Notch Signaling
- Authors
- Keskin, S., Devakanmalai, G.S., Kwon, S.B., Vu, H.T., Hong, Q., Lee, Y.Y., Soltani, M., Singh, A., Ay, A., Özbudak, E.M.
- ID
- ZDB-PUB-180517-7
- Date
- 2018
- Source
- Cell Reports 23: 2175-2185.e4 (Journal)
- Registered Authors
- Devakanmalai, Sheela Sundaram Gnanapackiam, Hong, Qiyuan, Ozbudak, Ertugrul
- Keywords
- cell signaling, clock, heterogeneity, mathematical modeling, noise, pattern formation, segmentation, stochastic, systems biology, time delay
- MeSH Terms
-
- Animals
- Biological Clocks/genetics*
- Body Patterning/genetics*
- Gene Expression Regulation, Developmental
- Mesoderm/embryology
- Mesoderm/metabolism
- RNA/genetics
- RNA/metabolism
- Receptors, Notch/metabolism*
- Signal Transduction*
- Somites/embryology
- Time Factors
- Zebrafish/embryology*
- Zebrafish/genetics*
- PubMed
- 29768214 Full text @ Cell Rep.
Citation
Keskin, S., Devakanmalai, G.S., Kwon, S.B., Vu, H.T., Hong, Q., Lee, Y.Y., Soltani, M., Singh, A., Ay, A., Özbudak, E.M. (2018) Noise in the Vertebrate Segmentation Clock Is Boosted by Time Delays but Tamed by Notch Signaling. Cell Reports. 23:2175-2185.e4.
Abstract
Taming cell-to-cell variability in gene expression is critical for precise pattern formation during embryonic development. To investigate the source and buffering mechanism of expression variability, we studied a biological clock, the vertebrate segmentation clock, controlling the precise spatiotemporal patterning of the vertebral column. By counting single transcripts of segmentation clock genes in zebrafish, we show that clock genes have low RNA amplitudes and expression variability is primarily driven by gene extrinsic sources, which is suppressed by Notch signaling. We further show that expression noise surprisingly increases from the posterior progenitor zone to the anterior segmentation and differentiation zone. Our computational model reproduces the spatial noise profile by incorporating spatially increasing time delays in gene expression. Our results, suggesting that expression variability is controlled by the balance of time delays and cell signaling in a vertebrate tissue, will shed light on the accuracy of natural clocks in multi-cellular systems and inspire engineering of robust synthetic oscillators.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping