Understanding of FMCD Postnatal Pathologies at Molecular Levels

Abstract

Focal Malformations of Cortical Development (FMCD) is one of the major cause of drug-resistant pediatric epilepsy. Developmental pathologies of the disorder have been well investigated in previous studies, but the mechanisms associated with more critical postnatal pathologies, including intractable epilepsy should be studied further for efficient treatment. To identify the molecular mechanisms leading to postnatal pathologies, we performed RNA-seq transcription profiling of human induced pluripotent stem cell (hiPSC)-derived neural cells (NC) with AKT3 p.E17K, a FMCD-causing genetic mutation. We listed differentially expressed genes (DEGs) and formed their network by protein-protein interaction, and found 1) extracellular matrix (ECM)-associated network and 2) synaptic function-associated network. Interestingly, DEGs from ECM network were strongly overlapped with the results of the developmental pathology study, but DEGs from synaptic function network were not. This result suggests that there are stage-specific mechanisms, and the synaptic function network might be associated with postnatal pathologies. We will verify this possibility in vitro and in vivo FMCD models. The discovery of postnatal stage-specific mechanism will provide key insights for epilepsy treatment in FMCD.