Heat stress-induced genomic instability in neural stem cells and its association with neuronal developmental deficits

Our findings reveal that hyperthermia impairs neuronal development through a "double-hit" mechanism. The "first hit" is an acute disruption of developmental programming via a p53-p21-mediated response to DNA damage. The "second hit" consists of permanent "genomic scars"-including SNPs and gene fusions-that can irreversibly alter the function of critical neurodevelopmental genes. By demonstrating that a transient environmental stressor can induce lasting genomic instability in neural progenitors, this study provides a compelling mechanistic framework linking maternal fever to the etiology of neurodevelopmental disorders and highlights a potentially crucial pathway for gene-environment interactions in brain development.