Subpopulations of interneurons (green) in a section of a mouse hippocampus. Image credit: NICHD (CC BY 2.0)
The brain harbors an astounding diversity of interconnected cells. Each cell contains the same basic set of genetic instructions, but only a fraction of the genome is used in each cell to assemble proteins. This selective gene expression gives rise to each cell’s characteristic properties, such as their shape and location, or whether they can activate or inhibit neighbouring cells.
How these defining features are encoded on a genetic level and selectively activated in cells to produce such diversity in the brain is not fully understood. One way to study gene expression in single cells involves profiling the transcriptome, the full range of intermediary RNA molecules a cell produces from its genes to make proteins.
Zhang et al. used transcriptome profiling to better understand how thousands of regulatory genes encoding regulatory proteins called transcription factors create different types of neurons in the zebrafish brain, which is similar to but much simpler than the human brain. To do so, they analysed transcriptome data extracted from cell populations located in specific brain regions and displaying different properties.
Zhang et al. identified distinct clusters of neurons in the larval zebrafish brain. Mathematical models then analysed the transcriptome profiles of these neuronal clusters with characteristic features. They revealed that neurons with similar characteristics did not necessarily share the same transcription factors. In other words, distinct sets of transcription factors gave rise to the same types of cells. Zhang et al. described this observation as a ‘convergent’ pattern. On the contrary, some neurons with dissimilar features expressed the same sorts of transcription factors, suggesting a ‘divergent’ developmental pattern also exists.
In summary, this work sheds light on variable gene expression patterns akin to design principles that shape neuronal diversity in the brain. It gives a new appreciation of how neuronal subtypes result from a complex set of regulatory factors controlling gene expression.
