The origins of the cortex

December 17th 2018

The Royal Academy of Science has awarded the Julien and Nora Fautrez-Firlefijn prize to Professor Eric Bellefroid, in recognition of the work completed by his team on some transcription factors in the developing cerebral cortex.

ULB's Developmental Genetics laboratory, under the direction of Professor Eric Bellefroid, studies neural stem cells. During the embryo's development, these cells proliferate and differentiate, forming what will eventually become the brain. ‘We look into the molecular mechanisms that control this proliferation and differentiation’, explains Professor Bellefroid. ‘In particular, we study the role of certain transcription factors. These are proteins that bind to specific DNA sequences in our genome, activating or repressing the expression of a series of genes that code for other proteins. These other proteins either maintain cells in proliferation or enable them to differentiate and to acquire a specific identity.

Transcription factors
Since 2013, Professor Bellefroid and his team have been studying the role of the transcription factors DMRT5/DMRTA2 and DMRT3 in the development of the mouse's brain. These factors are expressed only in the dorsal part of the telencephalon, which is the rearmost vesicle in the neural tube of a developing embryo, and eventually becomes the cerebral cortex, one of our brain's major structures, home to the cognitive functions.
By genetically disabling one or both of these transcription factors, researchers had already shown that they are essential growth regulators of the cerebral cortex. By overexpressing the transcription factors, they found that their concentration in the progenitor cells of cortical neurons also plays a key role in the specification of the various regions of the neocortex (e.g. motor, sensory, visual).

Revealing a new function
The latest results published by the research team in The Journal of Neuroscience(1) provide a little more insight into the complex role of these transcription factors. They show that in cortical progenitors, these factors cooperate with one another and with other transcription factors in order to block the expression of genes that determine ventral neural structures; thus, they define which cells are dorsal or ventral within the telencephalon. The study thus reveals a new major function of transcription factors DMRT3 and DMRT5 at a very early stage of our brain's development.

A ‘pain gene’
In addition to research on DMRT transcription factors in the cortex, the Developmental Genetics laboratory has been studying another factor: PRDM12. ‘In adults, the PRDM12 gene is expressed very selectively in nociceptors, which are neurons in the peripheral nervous system that are specialised in perceiving intense pain stimuli’, explains Professor Bellefroid. ‘We suspect that PRDM12 plays a part in acute and/or chronic pain.’?Should this hypothesis be confirmed, it could lead to new therapeutic approaches for pain management. In early 2019, the laboratory will start research work in order to validate PRDM12 as a therapeutic target for pain treatment(2).

(1) Desmaris E., ‘DMRT5, DMRT3, and EMX2 Cooperatively Repress Gsx2 at the Pallium-Subpallium Boundary to Maintain Cortical Identity in Dorsal Telencephalic Progenitors’ in J. Neurosci. 2018 Oct 17;38:9105-9121.
(2) This project, entitled PANOPP, will be conducted at ULB and UMons and is funded by the Walloon Region and an industrial partner.