The Role of AUTS2-Regulated Genes in Cell Cycle Progression: Insights into Neurogenesis

Abstract

The Autism Susceptibility Candidate 2 gene, known as AUTS2, encodes a protein with prominent association with several neurodevelopmental disorders through its roles in transcription regulation. However, the exact role of how AUTS2 influences neurogenesis remains not clear. Recent evidence showed that AUTS2 overexpression in the mouse neocortex contributes to cortical expansion and promotes neurogenesis during early brain development. Additionally, the AUTS2 upregulation was found to change the transcriptional landscape of neural progenitors, altering the expression of numerous genes during neurogenesis. This study explores the functional relevance of AUTS2-regulated genes in neural progenitor cells by siRNA mediated silencing of selected genes in U-2 OS cells to assess their role in cellular proliferation. The siRNA hits of candidate genes explored in the study were found to be upregulated upon AUTS2 overexpression in the mouse neocortex. Following gene silencing of these gene candidates, we performed colony formation assays and flow cytometry-based cell cycle analysis to validate their impact on cell cycle progression. Our findings reveal that the knockdown of our genes of interest leads to significant shifts in cell cycle distribution, characterized by an elevated number of cells halted in the G0/G1 phase, with a corresponding reduction in the S phase. Furthermore, we integrated data from BrainSpan Atlas to examine the expression patterns of our candidate genes in the human developing cortex, revealing marked enrichment in neurogenic niches. Overall, the project provides new insights into the possible involvement of genes: TICRR, ADAMTS10, TRRAP, NACC1, and HEATR1 in neural progenitor cell cycle progression.

Date of Award	2025
Original language	American English
Awarding Institution	HBKU College of Health & Life Sciences