The brain expresses genes in advance like a person prepares meals ahead of time - A culinary analogy to explain neuroscience

[Graça Marques, Catarina Homem]

In a recent study published in the journal PLOS Biology, researchers from NMS led by Catarina Homem discovered that several neuronal genes begin to be expressed long before they are needed by neurons and until that point, they are kept on standby.

Graça Marques, postdoctoral researcher at the investigadora pós-doutorada do laboratório Proliferation and Fate Regulation of Stem Cells led by Catarina Homem, explained that in the fruit fly, called Drosophila, young neurons already show age-related differences. Interestingly, these neurons, even when very young, already express genes necessary for communication between themselves, called neurotransmitter genes, which are only used several days later.

Understanding how neurons evolve from their birth is extremely important for being able to produce neurons for use in regenerative medicine, for example. Although the study of the early stages of neuronal development is essential, it has been an underexplored area until now, and therefore, the researchers delved into it in this recently published work.

To better understand this study, let's compare the functioning of the brain to a meal and imagine that a freshly prepared meal corresponds to a fully formed brain with its complete functional circuit.

Normally, genes (DNA) are expressed (transformed into mRNA) and then translated into proteins, which immediately perform their intended function. This would be equivalent to the cook having the ingredients, preparing them, and immediately cooking the meal, making it ready to be eaten.

In this study, the researchers discovered that genes associated with neurotransmitters, whose function is to facilitate communication between neurons, begin to be expressed shortly after the birth of a neuron but remain in a waiting state for several days without being translated into proteins until a later time, closer to when they will be needed for the proper functioning of the brain. In culinary terms, this process is similar to preparing the ingredients the cook will need weeks or even months in advance, storing them and leaving the final preparations, including cooking, for later, just before mealtime.

To study neuron maturation and the expression of these genes, the researchers conducted their investigation in fruit fly brains. This research found that the RNA of genes associated with neurotransmitters in cholinergic, glutamatergic, and dopaminergic neurons begins to be expressed in larvae but is only translated and used in pupae, several days later in the fly's life cycle. In humans, this waiting period would be equivalent to these genes being used approximately three years later.

Just as pre-preparation of meals can help optimize time and effort when cooking, this mechanism may be an excellent way to optimize brain function and have all components ready to be quickly used when needed. Why these genes are expressed so far in advance is still unclear.

Graça Marques and Catarina Homem also point out unanswered questions that need to be studied in the future. Specifically, how are genes associated with neurotransmitters kept untranslated in mRNA, which is very unstable, until a specific stage of development? In other words, how do we handle and store food so that it is ready to be cooked when we want to eat? Why is the RNA of these genes expressed so far in advance? In other words, why does the cook start preparing the meal long before serving it? And also, what triggers the expression of proteins associated with neurotransmitters? That is, how does the cellular cook decide when to start preparing the meal and how does it do it?

This work, led by the team at NMS, was done in collaboration with Nikolaos Konstantinides (Université de Paris, CNRS, Institut Jacques Monod, Paris, France) and with Patrícia H. Brito (NOVA School of Science and Technology).

The complete article, Asynchronous transcription and translation of neurotransmitter-related genes characterize the initial stages of neuronal maturation in Drosophila, can be found in the journal PLOS Biology.