Glia, which constitutes astrocytes and oligodendrocytes, are the most proliferative and abundant cell types in the central nervous system. Abnormal development of astrocytes and oligodendrocytes is associated with a number of neurological diseases and disorders such as amyolateral sclerosis (ALS), multiple sclerosis (MS), autism, epilepsy, schizophrenia, and glioblastoma, the deadliest of brain cancers. The basic-helix-loop-helix (bHLH) transcription factors Ascl1 and Olig2 are crucial for the specification and development of both astrocytes and oligodendrocytes, and are highly expressed in glioblastoma. The proposed project aims to: 1) determine the role and function of Ascl1 and Olig2 in regulating the generation of astrocytes and oligodendrocytes in the gray matter and white matter in the spinal cord; 2) determine the in vivo requirement of Ascl1 and Olig2 in brain tumors of a mouse model of glioblastoma; and 3) utilize Next-Generation sequencing techniques to identify on a genome-wide scale the DNA-binding profiles and direct transcriptional target genes of Ascl1 and Olig2 in glial progenitors in comparison to tumor cells of the glioblastoma mouse model. The culmination of this study will lead to new insights on the genetic regulatory networks of glial heterogeneity and glioblastoma development in the central nervous system.
Glial cells are the most proliferative and abundant cell types in the central nervous system. Abnormal development of glial cells is associated with a number of neurological diseases and disorders such as amyolateral sclerosis (ALS), multiple sclerosis (MS), autism, epilepsy, schizophrenia, and glioblastoma, the deadliest of brain cancers. The propose studies utilize advance genetic techniques to investigate the role of two regulatory proteins (Ascl1 and Olig2) in regulating the development of glial cells and glioblastoma in the brains of mice. Results from these studies will lead to new insights on the process of glial cell generation in different parts of the central nervous system and the progression of glioblastoma, and potentially, the development of regenerative medicine to treat and combat neurological diseases and cancers.
| Kelenis, Demetra P; Hart, Emma; Edwards-Fligner, Morgan et al. (2018) ASCL1 regulates proliferation of NG2-glia in the embryonic and adult spinal cord. Glia 66:1862-1880 |
