Étude des mécanismes physiopathologiques des hétérotopies nodulaires périventriculaires associées aux mutations des gènes FAT1 et FLNA
Léa Corbières – Team Cortical Development

Abtract
Periventricular nodular heterotopia (PVNH) is a cortical malformation characterized by ectopic neurons lining the ventricles. Clinically, PVNH is associated with epilepsy, autism spectrum disorders, and cognitive deficits. Epileptic seizures primarily originate from the adjacent normotopic cortex or in association with the heterotopia, suggesting that disruptions in cortical circuits could promote their onset. During my thesis, I demonstrated that Flna, a gene involved in the etiology of PVNH, regulates spinogenesis and dendritogenesis via the Rac1-Cofilin signaling pathway. Although many causative genes for PVNH have been identified, the genetic origin of 70% of sporadic cases remains unknown. Thus, through whole-exome sequencing of a clinical case of bilateral PVNH, we identified compound heterozygous missense mutations in the gene encoding the atypical cadherin FAT1. My thesis revealed a new role of Fat1 in neuronal migration, dendritogenesis, and the establishment of cortical layers. In summary, my research highlights the crucial roles of Fat1 and Flna in cortical layer organization and neuronal maturation, contributing to a new understanding of the pathophysiological mechanisms associated with PVNH.

Keywords
Cortical development, Neuronal migration, Maturation, PVNH, In utero electroporation

Jury
Alessandra Pierani, Rapporteuse – Institut Imagine & IPNP, Paris
Alexandre Baffet, Rapporteur – Institut Curie, Paris
Sara Bizzotto, Examinatrice – ICM, Paris
Françoise Helmbacher, Examinatrice – IBDM, Marseille
Christophe Porcher, Président – Inmed, Marseille
Carlos Cardoso, Directeur de thèse – Inmed, Marseille

Friday December 13th at 2:30 pm – Inmed room conference