The mechanism of Zbtb18 in interneurons progenitors and Glioblastoma

The brain cortex composition depend on precisely synchronized production and correct migration of diverse neuron populations, mainly glutamatergic neurons and GABAergic interneurons. This process is controlled by the spatiotemporal activity of transcription factors and their regulatory elements. Several studies had shown that haploinsufficiency of multiple genes associated with human neurodevelopmental disorders, including the transcription suppressors Zinc Finger and BTB Domain Containing 18 (Zbtb18) and Forkhead Box G1 (Foxg1). In MGE interneurons progenitors ZBTB18 acts as a cell cycle exit regulator, in which interneurons progenitors are differentiated into GABAergic interneurons. In contrast FOXG1 in neural progenitors consider to enhance proliferation and precocious differentiation. Interestingly, although they appears to have opposite roles in interneurons progenitors it was founds that ZBTB18 interact with FOXG1, to control gene expression in mature glutamatergic neurons. Moreover, loss of ZBTB18 was found to be connected with glioblastoma patient’s poor prognosis, while FOXG1 is highly expressed in glioblastoma, which is found to be important for tumor growth. My hypothesis is that in interneurons progenitors the level of expression of those two factors operate as a switch between proliferation and differentiation and disruption of their activity leads to glioblastoma. I aim to elucidate the overall mechanism of ZBTB18 and specifically its possible relationship with FOXG1 by generating two stable lines of U251 and mouse MGE cells infected with two lenti Zbtb18 tag V5 over-expression plasmids with inducible or constitutive expression. After calibration of the ZBTB18/V5/FOXG1 antibodies via western blot, ChiP-seq using these antibodies will be performed for targets identification.