A research team led by Susan Dymecki, an HMS professor of genetics, has reported that serotonergic neurons, which help regulate such processes as mood, appetite, breathing rate, and body temperature, come in at least six major molecular subtypes defined by distinct expression patterns of hundreds of genes. Using a mouse model, the researchers also found that the subtypes vary in their developmental lineage, anatomical distribution, combinations of receptors on the cell surface, and electrical firing properties.
Perhaps of greatest interest, the team showed that a serotonergic neuron’s gene expression and function depend not only on its location in the adult brain stem, but also on its cellular ancestor in the developing brain. Their report appears in the November 18, 2015, issue of Neuron.
“This work reveals how diverse serotonin neurons are at the molecular level,” says Benjamin Okaty, a postdoctoral researcher in the Dymecki lab and co-first author of the paper, “which may help to explain how, collectively, they are able to perform so many distinct functions.”
Adds Dymecki, “To have the list of molecular players that make each of these subtypes different from one another gives us an important handle on learning more about what that cell type does and how we can manipulate only that subtype. It holds enormous therapeutic potential.”
Although the work was done using an animal model, Dymecki is optimistic that it will be replicated in humans because the serotonergic neuronal system is in a highly conserved region of the brain, meaning that it tends to remain consistent across vertebrate species. Because of this, researchers can look for the same molecular signatures in human tissue and begin to tease apart whether particular subtypes of serotonergic neurons are involved in conditions such as sudden infant death syndrome or autism.
Such research could ultimately reveal previously unknown contributions of the serotonergic neuronal system to disease, inform the development of biomarkers, and lead to more targeted therapies.
The team’s findings could also inform stem cell research. “Which subtype of serotonergic neuron are we getting when we use current stem cell protocols?” Dymecki asks. “Can we drive the development of different subtypes? Can we watch how gene expression patterns change over time during development for each subtype?”
Image: James Cavallini/Science Source