The ssDNA binding protein FUBP1 was originally characterised as a transcriptional activator of the MYC oncogene. Surprisingly, however, FUBP1 loss-of-function is predicted to drive the primary brain cancer, oligodendroglioma. Here we aim to understand mechanisms underlying FUBP1’s unexpected tumour suppressive function in the brain. As a major impediment to improved glioma treatment is a lack of understanding of the interaction between glioma stem cells and their glial microenvironment, our study takes advantage of the conservation of FUBP1 (Psi) in Drosophila to study the neural stem cell-glia interaction in vivo. Thus, we aim to elucidate FUBP1/Psi function not only in neural stem cells but also in the cortex glial microenvironment, or niche, providing the structural support and secreted signals required for stemness and differentiation. Our preliminary data demonstrate FUBP1/Psi is critical in the cortex glia niche for preventing neural stem cell expansion. To better understand how FUBP1/Psi functions non-autonomously to control neural stem cell fate we used Targeted DamID (TaDa) to identify direct, genome-wide targets in the cortex glial niche. Intersection of direct FUBP1/Psi targets, with genes differentially expressed in Psi-depleted cortex glia identified secreted factors (ligands to the EGF receptor) and cell adhesion proteins, which we predict will function in cortex glia to control fate of neighbouring neural stem cells. Together, our data demonstrate FUBP1/Psi normally acts extrinsically in the glial microenvironment to prevent neural stem cell renewal and promote differentiation. Thus, we predict FUBP1 loss-of-function drives tumourigenesis, at least in part, by dysregulating glial-stem cell interactions.