Neural development involves the progression of proliferating cells to mature neurons in order to form a complete and precisely functioning central nervous system. The balance of proliferating and differentiating cells are in part controlled by changes in the expression of transcription factors, and the SoxB and C family TFs are integral to this process. Sox11, a member of the SoxC subfamily, has been shown to play a critical role in multiple steps of neural development including: establishment of neuronal identity and promotion of neural differentiation and maturation. Misregulation and loss of Sox11 function have been linked to various diseases and neurodevelopmental disorders including cervical cancer, mantle cell lymphoma and Coffin-Siris Syndrome (CSS), a disorder characterized by developmental disability and digit, facial and cardiac anomalies. Despite Sox11's significant role in development, little is known about the molecular mechanisms underlying its expression or function. In order to understand how Sox11 has different functions at different times in the development of the CNS, we will determine 1) the mechanism by which Sox11 drives the expression of distinct spatial- temporal gene targets and 2) the transcriptional and post-transcriptional mechanisms of regulation during neurogenesis. These goals have led us to identify the Sox11 partner protein interactions in space and time through development and the factors involved in controlling the dynamic expression of Sox11.
Developing new treatments for brain damage and neurodegenerative diseases requires a better understanding of how stem cell-like properties are regulated in the central nervous system and how progenitor pool expansion and neuronal differentiation are coordinated. While many of the players in these processes are known, their relationships to other proteins in the pathways, their mechanisms of action and direct targets are unknown. This proposal characterizes the function of Sox11, a transcription factor integral to the development of the central nervous system and to the maintenance of a balance of neural progenitors and neurons.
