par Dannawi, Maya 
Président du jury Vanhamme, Luc
Promoteur Bellefroid, Eric
Publication Non publié, 2024-04-26
Président du jury Vanhamme, Luc
Promoteur Bellefroid, Eric
Publication Non publié, 2024-04-26
Thèse de doctorat
| Résumé : | The Prdm12 gene encodes the first transcriptional regulator that, once mutated, causes congenital insensitivity to pain (CIP) in humans. In recent years, epigenetic mechanisms have opened an avenue for the development of novel kind of analgesics. Work of our laboratory has shown that in mice, during development, Prdm12 is strongly expressed in somato-sensory ganglia where it is selectively transcribed in neurons from the nociceptive lineage, and that it remains expressed in mature neurons where it controls nociception. However, its mechanisms of action remain largely unknown. In my work, we have investigated the mechanisms behind Prdm12’s role in the specification of the nociceptive lineage in nervous system development. Results obtained have confirmed that Prdm12 is required for progenitor survival. They also revealed that it is required in developing somato-sensory neuron to repress an alternate viscero-sensory fate. Using a transgenic mouse line of Prdm12 overexpression in an inducible conditional manner, we showed that Prdm12 does not block Phox2b expression when ectopically expressed in visceral ganglia, revealing a context dependent repressive function. Previous work from the lab showed that the loss of Prdm12 in mature nociceptors of adult mice deregulates the expression of many nociceptive genes, and reduces their response to capsaicin. A hypersensitivity to formalin was also observed. To further approach the role of Prdm12 in nociception, we performed complementary Prdm12 gain of function experiments using AAV. The preliminary results obtained further suggest a role for Prdm12 in nociception. |
