• FOXG1
• Stem cells
• Zika virus

The brain is the most complex and enigmatic organ of our body, its formation and development need extended time and a fine regulation. These aspects make the brain susceptible to many insults that might disrupt the normal development. In particular, the neocortex is structured and organized by a complex mechanism defined “inside out”, during which different cellular types are generated from neural stem cells (NSCs). Many neurological and psychiatric disorders occur because of alterations in these processes for environmental or genetic causes. Among the latter, are the congenital infections of central nervous system, for example pathologies caused by viruses belonging to the TORCH group, neurotropic and teratogenic agents. Following the 2015 outbreak in Brazil, Zika virus (ZIKV) has been added to this group. ZIKV is a viral agent able to cause severe neurodevelopmental impairments, including microcephaly, defined “Congenital Zika Syndrome” (CZS). Among the congenital causes of microcephaly, particularly interesting are the mutations of the transcriptional factor Forkhead box g1 (FOXG1). This protein is required for proper telencephalon and cortical development and many mutations are responsible for the “FOXG1-related disorders”, a spectrum of neurodevelopmental disorders, including microcephaly, intellectual disability, and cerebral malformation.
In this thesis we investigated a possible functional alteration of FOXG1, with subsequent neurodevelopmental dis-regulation, as a consequence of ZIKV infection. Previous studies demonstrated that ZIKV infects mainly NSCs, therefore for our work we chose an in vitro model based on human neural precursors cells derived from induced pluripotent cells (hiPS-NPCs), by using a protocol of neural induction based on “Dual SMAD inhibition”. Generated hiPS-NPCs were infected with ZIKV and analysed by immunofluorescence to observe a possible impact on FOXG1 after infection. Our observations suggest that, while in the control FOXG1 is localized mainly in nucleus, after infection it dislocates to the cytoplasm.
hiPS-NPCs use provided us an alternative model to the study of ZIKV and its effect on neurodevelopment, this has let us to highlight how an exogenous insult can affect function and localization of an endogenous transcriptional factor, fundamental for the cortical development.