The tempo of brain development
Why do some regions of the brain grow more than others? A recent discovery by Denis Jabaudon's laboratory shows that mitochondria – the energy powerhouses of our cells – influence the tempo at which neurons are born. And this tempo is not insignificant; it could play a role in psychiatric disorders.
Denis Jabaudon, professor and director of the Department of Basic Neurosciences at the Faculty of Medicine and member of its Synapsy Center for Neuroscience and Mental Health Research, leads a laboratory exploring the genetic mechanisms that orchestrate the generation of neurons and their integration into functional circuits during development. “Studying neurogenesis is a fundamental challenge”, explains Denis Jabaudon, “because, unlike other cells in the body, neurons produced during development accompany us throughout our lives.” Any alteration at this critical stage can therefore have lasting, even irreversible, repercussions.
But a new area of research has recently emerged: the tempo of brain development. By mapping the birth of neurons in mice, his team has identified a factor in brain formation that had previously been little explored: the role of mitochondria in regulating neurogenesis over time.
The first steps of the nervous system
Early in embryonic development progenitor cells proliferate to give rise to several types of specialised cells, such as neurons or glial cells. In mammals, the progenitor cells destined to form brain structures initially organise themselves into three morphologically similar vesicles: the forebrain, midbrain, and hindbrain. However, at the end of gestation, these once homogeneous structures give rise to brain regions of strikingly different sizes, with the forebrain having by far the biggest size: it gives rise to the cerebral cortex, a key structure of our species allowing us a conscious perception of the outside world.
By tracing the temporal evolution of progenitor cells in these three vesicles, Denis Jabaudon's team observed that, despite a common start in the development of the three vesicles, the hindbrain is characterised by cell division of progenitor cells resulting mainly in two neurons. Neurogenesis therefore occurs briefly and intensely. Conversely, in the forebrain, progenitor cells divide more often into one progenitor cell and one neuron, allowing the pool of progenitor cells to be maintained over time.
Mitochondria, the conductors of neurogenesis
To understand where this difference comes from, the laboratory looked at the genetic profile of progenitor cells from the three brain vesicles. In regions where neurogenesis occurs over a long period of time, this analysis revealed high expression of FAM210B, a mitochondrial protein that regulates the energy function of cells. To confirm the link between the gene and the observation, Denis Jabaudon's team inhibited FAM210B in vivo in these regions. Neurogenesis accelerated and total neuron production decreased. Conversely, activating this gene in regions where it is not normally expressed led to longer neurogenesis and a greater number of neurons than expected.
Denis Jabaudon explains: “The FAM210B gene modifies the metabolism generated by mitochondria. Mitochondria that express it are associated with slower energy metabolism, which produces more lactate. This type of metabolism promotes divisions that produce one to two progenitor cells.” This mechanism therefore maintains the reservoir of progenitor cells and promotes more consistent neuronal production.
A risk of cacophony
However, these results highlight a little-known vulnerability of the brain: its need to respect the tempo specific to each region to develop properly. Even a slight delay can lead to an imbalance in the formation of brain regions and their connections. For Denis Jabaudon, this is where this work ties in with another of his laboratory's research theme: understanding how neurons organize themselves into coherent circuits. “The brain cannot just make the right neurons,” he explains. “It also has to produce them at the right time so that connections are established with precision.”
Disruptions in this timing could explain certain forms of psychiatric disorders, where brain circuits appear intact but function in a disorganised manner. This discovery thus opens up a new avenue of inquiry: what if these disorders arise from a temporal cacophony rather than a structural defect?
10 Jun 2025