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 because of a changed extracellular environment. The identification of novel factors responsible for regulating NSC fate is necessary for the molecular understanding of NSC differentiation. In previous work, we have identified that fibrinogen, a blood-derived protein, which is deposited in the nervous system after perturbations of the neurovascular homeostasis, is an inhibitor of neuronal regeneration and an activator of astrocyte scar formation. Fibrinogen interacts with a plethora of receptors and mediates pathways that control cell proliferation and differentiation. Although the signalling machinery necessary for fibrinogen action is present in brain cells, such as NSCs, the role of fibrinogen on NSC differentiation has not been characterized. The central goal of this project is to understand the molecular basis of fibrinogen signalling on NSC proliferation, migration and differentiation. The studies in this project involve the identification and characterization of the NSC/progenitor cell populations, the receptors and signaling mechanisms used by fibrinogen to mediate its effects on regulating NSC fate using state-of-the-art in vivo and in vitro techniques. Understanding how fibrinogen affects neurogenesis at the cellular and molecular levels after CNS injury is important for developing novel therapeutic approaches to promote functional regeneration of the nervous system.
Fields of science
Call for proposal
See other projects for this call