PUBLICATION
Cell coupling compensates for changes in single-cell Her6 dynamics and provides phenotypic robustness
- Authors
- Doostdar, P., Hawley, J., Chopra, K., Marinopoulou, E., Lea, R., Arashvand, K., Biga, V., Papalopulu, N., Rodriguez, X.S.
- ID
- ZDB-PUB-240429-13
- Date
- 2024
- Source
- Development (Cambridge, England) 151(10): (Journal)
- Registered Authors
- Chopra, Kunal, Lea, Roberto, Papalopulu, Nancy
- Keywords
- Her6, Neurogenesis, Oscillations, Telencephalon, Zebrafish
- MeSH Terms
-
- Animals
- Basic Helix-Loop-Helix Transcription Factors*/genetics
- Basic Helix-Loop-Helix Transcription Factors*/metabolism
- Cell Differentiation
- Gene Expression Regulation, Developmental
- Phenotype*
- Receptors, Notch/genetics
- Receptors, Notch/metabolism
- Signal Transduction
- Single-Cell Analysis
- Telencephalon/embryology
- Telencephalon/metabolism
- Zebrafish*/embryology
- Zebrafish*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 38682303 Full text @ Development
Citation
Doostdar, P., Hawley, J., Chopra, K., Marinopoulou, E., Lea, R., Arashvand, K., Biga, V., Papalopulu, N., Rodriguez, X.S. (2024) Cell coupling compensates for changes in single-cell Her6 dynamics and provides phenotypic robustness. Development (Cambridge, England). 151(10):.
Abstract
We investigate the effect of altering the protein expression dynamics of the bHLH transcription factor Her6 at the single-cell level in the embryonic zebrafish telencephalon. Using an homozygote endogenous Her6:Venus reporter and 4D single-cell tracking, we show that Her6 oscillates in neural telencephalic progenitors and that fusion of protein destabilisation domain (PEST) alters its expression dynamics, causing most cells to downregulate Her6 prematurely. However, counterintuitively, oscillatory cells increase with some expressing Her6 at high levels, resulting in increased heterogeneity of Her6 expression in the population. These tissue-levels changes appear to be an emergent property of coupling between single-cells as revealed by experimentally disrupting Notch signalling and by computationally modelling alterations in Her6 protein stability. Despite the profound differences in the single-cell Her6 dynamics, the size of the telencephalon is only transiently altered, and differentiation markers do not exhibit significant differences early on, while a small increase is observed at later developmental stages. Our study suggests that cell coupling provides a compensation strategy, whereby an almost normal phenotype is maintained even though single-cell gene expression dynamics are abnormal, granting phenotypic robustness.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping