Underlying Molecular Mechanisms of Gliogenesis and Gliomagenesis in the Central Nervous System

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 DESCRIPTION (provided by applicant): 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.