Investigating Tumor Growth and Regulation in Supratentorial Ependymomas; The Impact of Dlk1 and Egr1 Knockout

Ependymomas (EPNs) are primary brain tumors that often arise from radial glial cells lining the ventricular system. Supratentorial ependymomas (ST-EPNs) are particularly aggressive, and understanding the molecular factors driving their growth is critical for developing targeted therapies. This study investigates the roles of DLK1 and EGR1, key regulators in cellular differentiation and tumorigenesis, in the development of ST-EPNs. We utilized genetically engineered mouse models to induce postnatal knockouts of DLK1 and EGR1 and evaluated tumor growth using histological and imaging techniques. Tumor area was quantified across multiple brain sections from both male and female mice. DLK1 knockout brains exhibited consistent tumor growth in both sexes, suggesting that DLK1 may not play a critical role in tumor formation. It is likely that the Notch signaling pathway, normally activated by DLK1, remains activated through other ligands, such as Jagged1, compensating for the loss of DLK1. In contrast, EGR1 knockout brains showed no tumor formation in either male or female mice, indicating that EGR1 is essential for ST-EPN development. Gender analysis indicated no significant differences in tumor growth, suggesting that DLK1’s influence on tumor progression operates independently of sex-specific factors. These findings provide preliminary insights into the complex role of DLK1 and EGR1 in ST-EPN tumorigenesis, highlighting the need for further investigation into their interaction and potential as therapeutic targets. Future studies should address the limitations of small sample sizes and explore combinatorial knockouts to better understand their roles in tumor growth.