Le mardi 14 octobre 2025, Monsieur Nicolas LAMBERT, titulaire d'un Master en médecine et d’un Certificat de formation à la recherche en sciences biomédicales et pharmaceutiques, présentera l'examen en vue de l'obtention du grade de Doctorat en sciences biomédicaleset pharmaceutiques, sous la direction de Monsieur Laurent NGUYEN.

Cette épreuve consistera en la défense publique d'une thèse intitulée : "Contribution to the Understanding of Cerebral Cortex Development and Associated Malformations by Investigating the Role of NEDD4-2 in the Migration of Cortical Interneurons".

Le jury sera composé de :

Vincent BOURS (Président), Bert BRONE (UHasselt), Ira ESPUNY CAMACHO, Fiona FRANCIS (Inst. Fer à Moulin), Brigitte MALGRANGE, Pierre MAQUET, Laurent NGUYEN.

Résumé de la thèse

Cerebral cortex development proceeds through a sequential progression of tightly regulated biological processes governed by molecular pathways, with ubiquitination playing a critical role in maintaining this regulation. NEDD4-2, an E3 ubiquitin ligase, has been implicated in malformations of cortical development (MCDs) through specific mutations, which are also associated with a spectrum of other phenotypic abnormalities, including neurodevelopmental delay, syndactyly of the 2nd and 3rd toes, visual impairments, and epilepsy.

Using two mouse models, we investigated the role of NEDD4-2 in the migration of cortical inhibitory interneurons and analyzed the impact of MCD-associated mutations on this process. Our findings revealed that both the loss of NEDD4-2 and its mutation lead to defects across all stages of interneuron migration, including branching, organelle translocation, and nucleokinesis. Furthermore, we identified cellular mechanisms underlying these migration defects, characterized by abnormalities in cytoskeleton dynamics.