Microscopy image showing photoreceptors cells (yellow) in the outermost layer of the mouse retina and bipolar cells (red) in the layer below. Image credit: Daniel Murphy (CC BY 4.0)
Humans see the world through a light-sensitive tissue at the back of the eye called the retina, which is made up of three layers that each contain specific cell types. The layers form a circuit, with light-sensing photoreceptor cells in the outermost layer connected to bipolar cells in the middle layer, which connect to the brain via specialized cells in the innermost layer. Photoreceptors and bipolar cells share similar characteristics and are thought to be ‘sister cells’ which evolved from a common ancestral cell type. However, it is not well understood how these two cells types diverged during evolution.
Every cell type has a specific role, which is largely determined by the set of genes that it switches on or off. Specialized regions of DNA, called enhancers, determine whether a gene is turned on or off in a particular cell type. In each cell, DNA strands are bundled together with proteins into a coiled structure known as chromatin. In some cells, a particular enhancer may be ‘shut down’ and rendered inactive on account of being tightly packed within chromatin. Whilst in other cells, the same enhancer may be ‘open’ and ready for action. For a given cell type, which genes are turned on is determined, in part, by which enhancers are open.
One way to distinguish between cells is by examining how their chromatin is packaged to see which enhancers are open. Researchers have previously characterized the chromatin structure of photoreceptor cells, but the structure of chromatin in bipolar cells, and how it compares to that of photoreceptors, remained unknown. Now, Murphy et al. have examined the chromatin profile of bipolar cells from the mouse retina in order to gain a better understanding of how these two cell types may be evolutionarily related.
The analysis revealed that although bipolar and photoreceptor cells switch on different sets of genes, the enhancers open in each cell type are very similar. Despite this similarity, Murphy et al. were able to detect subtle differences in short sequences of DNA, known as motifs, present in bipolar and photoreceptor enhancers. Further experiments showed that one of these motifs may be responsible for turning photoreceptor genes off in bipolar cells. This motif therefore appears to play a critical role in distinguishing photoreceptors from bipolar cells.
This comparison of photoreceptor and bipolar cells has provided a possible mechanism whereby photoreceptor and bipolar cells diverged in evolution from a single common ancestral cell type. This insight may help explain how complex organisms with many cell types may have evolved from a single-cell ancestor long ago.
