Zmiz1 Mutation Alters Gene Expression in the Prefrontal Cortex: Insights into ADHD

Publication Date

Spring 3-23-2026

Presentation Length

Poster/Gallery presentation

College

College of Sciences & Mathematics

Department

Psychological Sciences and Neurosciences, Department of

Student Level

Undergraduate

Faculty Mentor

Dr. Jinhee Park

Metadata/Fulltext

Metadata ONLY

Presentation Type

Poster

Summary

ADHD is a significant biological and medical condition that affects cognitive, behavioral, and executive-function processes in the human nervous system, often impairing attention, emotional regulation, and daily functioning. De novo mutations in Zmiz1 have been identified as a potential cause of a neurodevelopmental syndrome with features including ADHD. Zmiz1functions as a transcriptional co-activator and interacts with key neurodevelopmental regulators such as Notch1, p53, and Smad3/4. Its expression is enriched during embryonic cortical development, especially in apical progenitors, basal progenitors, and postmitotic neurons. Despite its strong association with human neurodevelopmental disorders, the specific role of Zmiz1 in brain development and how its disruption contributes to ADHD-related phenotypes remains unclear. In this study, I re-analyzed publicly available RNA-seq data from wild-type (WT) and Zmiz1 knockout (KO) mouse cortex to identify gene expression changes associated with ADHD in the prefrontal cortex, a brain region strongly involved in attention and executive control. Using a false discovery rate (FDR) cutoff of 0.01, 143 differentially expressed genes (DEGs) were identified at P1, while a total of 2,424 DEGs were identified at P14. Notably, gene expression changes were much more pronounced at P14 compared to P1, indicating that most gene changes happen at P14, with very little overlap with P1, suggesting strong stage-specific effects of Zmiz1. In addition, Venn diagram analysis further showed very limited overlap between the two stages, with only 54 shared genes, while 89 genes were unique to P1 and 2,227 genes were unique to P14. This suggests that Zmiz1-related gene regulation is highly stage-specific and becomes more pronounced at later developmental stages. Pathway enrichment analysis showed that many of these genes are involved in synaptic signaling, neurotransmitter regulation, neuronal development, and immune-related pathways. These findings suggest that ADHD may be associated with changes in how neurons communicate and develop in the brain. Overall, this study provides new insights into the molecular mechanisms underlying ADHD and highlights potential targets for future therapeutic approaches.

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