Characterizing the role of Lgl1 in Neural Stem Cells

Asymmetric cell division and cell migration are two critical components of neural stem cell differentiation and brain development. When dysregulated, they can lead to the development of glioma, a very common and lethal type of primary brain tumor with a very low survival rate (Mehta and Lo Cascio 2018). Gliomas predominantly arise from mutations in neural progenitor cells (Klezovitch et al. 2004). Neural progenitor cells (NPC cells) are tissue-specific multipotent adult stem cells. They are responsible for maintaining homeostasis as well as key cellular processes such as proliferation, migration and differentiation/growth. NPC’s self-renew through the process of asymmetric cell division, in which one NPC and one differentiated cell is produced when the cell divides. Lgl1, or lethal giant larvae 1, was first characterized in Drosophila neuroblasts in 1968 and was determined to be a tumor suppressor gene, with roles in regulating cell polarity and proliferation (Dahan et al. 2012). Lgl1 is an key regulator of asymmetric cell division and differentiation (Humbert et al. 2008). Thus, it is important to understand the role of Lgl1 in neural progenitor cells and the biochemical pathway behind these phenotypic changes in cell fate. The goal of my research is to explore how Lgl1 affects NPC behaviors and the underlying changes in the active biochemical pathways. Ultimately, these studies will help us further understand the role of Lgl1 in brain development, particularly its role in oligodendrocyte progenitor cells, and the resulting biochemical changes resulting from its knockout.