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Mechanism of action of Prdm12 throughout the development and implications in pain perception

par Sabaté San José, Alba
Président du jury Vanhamme, Luc
Promoteur Bellefroid, Eric
Publication Non publié, 2025-01-16

Thèse de doctorat

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Résumé :

Pain is an evolutionally conserved mechanism that alerts us from potential danger and is important for our survival. When the mechanisms behind pain perception become sensitized, pain becomes a burden that negatively impacts our quality of life. For years, the scientific and medical community have put major efforts to treat, cure or palliate the chronicity of pain. In this pursuit, a key area of focus is understanding the mechanisms behind pain perception. One promising approach is studying genes whose disruption leads to conditions like congenital insensitivity to pain (CIP), such as PRDM12.PRDM12 is a transcriptional regulator that is required for the development of nociceptors, the neurons that respond to noxious stimuli. PRDM12 is specifically expressed in mature nociceptors during adulthood, although its function in this stage remains unknown. In this thesis, I have first studied the role of PRDM12 in DRG of adult mice. Using inducible conditional Prdm12 knock-out mice, we observed that loss of PRDM12 in mature nociceptors affects the expression of a small subset of genes important for nociceptor function and modulates the behavioural response to pain. I next studied its mechanism of action. Therefore, using ChIP-seq experiments, I identified PRDM12 direct targets in embryonic DRG. The results obtained indicate that PRDM12 acts as a repressor during development to promote nociceptive cell fate. Finally, I also identified PRDM12 interacting partners that appears to be required for its function. Together, the results obtained further validate PRDM12 as a novel pain target.