Does a Cell’s Gene Expression Always Reflect Its Function?
- 3 days ago
- 3 min read
A Deep Dive into Zebrafish Neurons and the Complexity of Cell Identity.
Introduction
In modern biology, one of the most powerful tools is the ability to look inside a cell and the genes that are active. Technologies like single-cell RNA sequencing (scRNA-seq) allow researchers to group cells into types based on the RNA transcripts they express. This approach has brought about breakthroughs in tissue mapping, developmental biology and disease diagnosis.
But a fundamental question is now being asked with increasing urgency:
Does the collection of RNA transcripts in a cell, its transcriptome, accurately represent what the cell does?
Recent studies in zebrafish neurons have added a layer of complexity to this conversation. While two neurons might appear almost identical based on their gene expression, their actual behaviour to respond to stimuli, interact with their environment, and function within a neural circuit can be very different.
What Does Gene Expression Mean and How Is It Used to Categorise Cells?
The process by which information from a gene is utilised to create a useful product, such as a protein, is known as gene expression. A gene's DNA is converted to RNA when it is "turned on." A cell's identity and function can be inferred from the collection of all RNA molecules present at any one time, which also shows which genes are active.
The use of scRNA-seq to identify cell types has developed in years, as a result of this insight. For example, brain cells like neurons and glial cells or susceptible cells like T-cells and B-cells can often be clustered together.
Zebrafish Neurons: A Case Study in Functional Diversity
Zebrafish have become a favourite model organism in neuroscience due to their transparent embryos and relatively simple nervous systems. In a recent investigation, researchers analysed gene expression in developing zebrafish neurons and mapped it against the cells’ behaviours in live animals.
What they found was unexpected:
Neurons that were nearly indistinguishable at the transcriptomic level displayed strikingly different behaviours.
For example:
Some neurons responded to visual stimuli.
Others reacted to touch or mechanical changes.
Some are activated in response to movement or proprioceptive feedback.
All these neurons had highly similar gene expression profiles, suggesting they belonged to the same “cell type.” Yet, in terms of real-world function, they were distinct.
Why Does This Discrepancy Happen?
The mismatch between transcriptomic similarity and functional diversity can be explained by several biological factors:
1. Post-Transcriptional and Post-Translational Regulation
Even if two cells express the same mRNA, the final protein levels can vary. This is due to:
Differences in RNA stability or degradation
Variable rates of translation i.e the conversion of RNA to Protein.
Protein modifications like phosphorylation or methylation
Protein localization within the cell
2. Cellular Context and Microenvironment
A cell doesn’t operate in isolation. Its function is often influenced by:
Signals from neighbouring cells
Extracellular matrix interactions
Mechanical forces or environmental cues
This means that identical transcriptional programs can lead to different outcomes depending on external influences.
3. Neuronal Plasticity and Activity-Dependent Changes
Neurons, in particular, can adapt their function based on the signals they receive. Experience, sensory input, and neural activity can reshape synapses and signalling patterns, without drastically altering gene expression in the short term.
4. Developmental Stage and Timing
Two cells with the same transcriptomic snapshot may be at different points in their functional maturation. Gene expression might not yet reflect the functional specialisation that emerges later.
Conclusion
Defining a cell's identity by its RNA profile is like trying to understand a person's personal diary. It offers valuable clues, but it doesn’t tell you what they actually mean.
The zebrafish neuron studies remind us that function doesn't always follow form. To truly understand cells, especially in complex systems like the brain, we must go beyond the gene and explore the dynamic behaviours that shape life itself.
About the Author:
Janani J
Biotech Undergraduate
References
Cusanovich DA, Hill AJ, Aghamirzaie D, Daza RM, Pliner HA, Berletch JB, Filippova GN, Huang X, Christiansen L, DeWitt WS, Lee C. A single-cell atlas of in vivo mammalian chromatin accessibility. Cell. 2018 Aug 23;174(5):1309-24.
Zhang, Y., et al. (2022). Functional diversity of transcriptionally similar neuronal subtypes in the zebrafish hindbrain. Nature, 609(7925), 113–118.
Image Reference
Herget U, Gutierrez-Triana JA, Thula OS, Knerr B, Ryu S. Single-cell reconstruction of oxytocinergic neurons reveals separate hypophysiotropic and encephalotropic subtypes in larval zebrafish. ENeuro. 2017 Jan 1;4(1).
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