ETD

• Chikungunya virus
• Coxsackie B5
• FOXG1
• Herpes Simplex Virus 2
• Human Cytomegalovirus
• microcephaly
• neo-cortical neuroepithelial stem cells
• neural stem cells
• NPCs derived from hiPSCs
• TORCH pathogens

Congenital abnormalities, including microcephaly, can be caused by genetic mutations (e.g., FOXG1 gene) or environmental influences, such as infections by TORCH viruses (Toxoplasma, Rubella, CMV, HSV, and others). These teratogenic infections can be transmitted prenatally, perinatally, and postnatally, leading to severe neurodevelopmental syndromes, including congenital microcephaly, developmental delay, and prenatal death, by targeting NPCs. This creates an urgent need to uncover the molecular mechanisms underlying TORCH-induced microcephaly.
This study targeted the FOXG1 gene, which encodes a telencephalic transcription factor involved in NSC proliferation, self-renewal, and cell cycle progression. Mutations in this gene are also associated with developmental disorders, including microcephaly. We investigated the impact of three TORCH agents (HSV2, HCMV, COXB5) and one non-TORCH virus (CHIKV) on human NPCs, using NCX NES cells and hiPSC-NPCs as in vitro models.
Our findings indicate that TORCH infections disrupt FOXG1 nuclear localization in NPCs, leading to cell cycle alterations. This highlights the selective fragility of telencephalic NPCs to these viral impacts. It emphasizes the implications for transcription factor dynamics, cell cycle progression, innate immune response, and cell death.
In summary, this study clarifies the convergence and molecular and cellular consequences of genetic and environmental insults that impact CNS development.