The role of Id3 as a transcriptional regulator of neuronal differentiation in CNS injury of disease

• Applicant: Professor Christian Schachtrup, Ph.D.
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2012 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 208413883

After brain injury or neurologic disease, the ability of the central nervous system (CNS) to regenerate is limited. Neural stem cells (NSCs) have the potential to differentiate into neurons and glia, but neurogenesis is incomplete after CNS disease. The molecular mechanisms regulating neuronal differentiation are not understood. Inhibitor of DNA binding (Id) proteins are key regulators of neuronal differentiation during embryogenesis. We propose to characterize the role of Id3 during neuronal regeneration after injury or neurologic disease. Id3 protein expression is regulated by the TGF-β superfamily, which is up-regulated after blood-brain-barrier (BBB) opening. We will identify the spatial and temporal expression of Id3 in two mouse models with BBB opening: trauma and multiple sclerosis (MS). We will examine the transcriptional machinery Id3 utilizes to determine neuronal and glial fates in vitro and we will genetically inhibit Id3 protein in a mouse model of MS potentially identifying Id3 as a therapeutic target in CNS disease. Understanding the cellular and molecular mechanisms regulating neuronal differentiation in CNS disease is important for the development of novel therapeutic approaches that promote functional regeneration.

• DFG Programme: Research Grants