A key gene in embryonic development protects the adult brain's stem cell pool

Research from the Cajal-CSIC Neuroscience Center in Madrid has discovered a new mechanism that "controls how adult neural stem cells are generated" during the development of the dentate gyrus, a region of the hippocampus "key to memory and learning."

Specifically, the center reported this Thursday that they have discovered how neural stem cells (progenitors of neurons) " alternate between rest and activation ," an essential requirement for "preserving the brain's regenerative capacity throughout life." The discovery points to the Sox5 gene as the "guardian" of this cellular balance.

The study, led by Dr. Aixa Morales, head of the Molecular Control of Neurogenesis Laboratory, was conducted in mice and focuses on neural stem cells in the hippocampus, a brain structure involved in processes such as memory and learning. These neural cells remain in a "resting state known as quiescence," in which they are not mature cells nor do they divide to generate neurons, but in which they can be activated when necessary . This "resting" strategy ensures that they do not become exhausted prematurely.

What was not well understood until now was what "mechanisms ensure that the state of quiescence is correct and reversible." This work from the Cajal Neuroscience Center provides new insights , "demonstrating that the Sox5 gene is crucial for establishing this state of rest in a balanced manner."

Another relevant finding of the study is the identification of a critical time window during postnatal development, specifically in the second week after birth, in which the proper balance is established between two resting states of neural stem cells: a "deep" state, which keeps them inactive for long periods, and a "superficial" state, in which they are closer to being activated. During this time window, Sox5 limits the entry of neural stem cells into "superficial resting states," which makes them more likely to divide.

This regulation is essential to avoid "a temporary overproduction of neurons in youth," which could deplete the stem cell reserve and therefore " reduce the brain's capacity for regeneration in adulthood."