Rôles de Trio dans la migration des interneurones GABAergiques corticaux
Epilepsy can result from a loss of balance between the levels of excitation and inhibition in the brain. Epileptic seizures manifest themselves by uncontrolled limb movements and epileptic activity on brain wave recordings (EEG). Possible defects in the development of inhibitory neurons may cause an increased excitability of the brain cells and underlie such seizures. To better understand the genetic causes of epilepsy, the laboratory of Dr. Rossignol conducted a gene sequencing study of a large cohort of children diagnosed with infantile spasms, a severe form of early-onset epilepsy. Among the newly identified genes, sequencing revealed mutations in the TRIO gene. In the literature, this gene was already associated with intellectual disability and was noted as a vital participant for axonal guidance and cellular motility in various organisms. However, little is known about the role of this particular gene in the development of inhibitory neurons. The objective of the study is to investigate the roles of Trio in the migration of these inhibitory interneurons in mice by exploring the processes that lead to the migration of these inhibitory neurons to their final position. With the utilization of ex vivo electroporation and a shRNA driven by the Dlx5/6 promoter, we repressed the Trio gene in cortical GABAergic interneurons during the prenatal stages of mouse development. Our results demonstrate that the loss of function of the Trio gene in embryonic mice leads to defects in the morphology of inhibitory neurons and in a reduced number of interneurons reaching the cortical plate. Our rescue experiment suggests that defects in interneuron morphology might result from deregulation of the RhoA signalling pathway. Overall, our results expand our understanding of the roles of TRIO in the regulation of cortical circuits development.
Migration Trio Development Epilepsy Guanine nucleotide exchange factor Interneuron Migration Morphology Mouse Trio