Unraveling the genetic mechanisms of human neural differentiation and brain development

초록

We identified a gene critical for cellular stress responses and protein synthesis regulation, including UPR and ER stress. Mutations in this gene are linked to severe neurodegenerative diseases like Alzheimer's and microcephaly, as well as diverse human disorders. However, the specific functional impacts of these mutations in neurodevelopmental disorders require further investigation. Our study aims to elucidate the mechanisms governing human neural differentiation and brain development influenced by genetic alterations in specific genes, focusing on understanding their roles in cellular stress responses that affect brain development. To explore the functional consequences of genetic mutations, we introduced mutated cDNA versions of the gene into human cells using transfection and lentiviral infection methods. Biochemical analyses, including western blotting, were employed to assess the impact of these mutations on protein function. Additionally, CRISPR-Cas9 technology was utilized to generate knockout models, enabling the study of loss-of-function effects in cellular contexts. Our investigations revealed insights into how genetic alterations affect cellular stress response pathways, shedding light on potential mechanisms through which dysfunctional gene variants contribute to disease pathology. Integrate CRISPR-Cas9 with multi-omics screening using dual-fluorescent reporter hiPSCs to identify new genes in cellular stress responses. Validate their significance in neurodevelopment through in vitro and in vivo studies to uncover potential therapeutic targets.