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Title: Role of Rai/Shc C proteins in adult neural stem cells and progenitors
Author: Ortensi, Barbara
ISNI:       0000 0004 2674 2926
Awarding Body: The Open University
Current Institution: Open University
Date of Award: 2009
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Rationale. Rai-/- mice are less resistant to ischemic damage compared to the wild type mice. They show increased mortality and more neuronal apoptosis. This phenotype can be explained only in part with Rai-induced survival in mature neurons. In the last years neural stem cells (NSC) have been shown to play an essential role in the recovery of the brain upon ischemia, through their mobilization, migration toward the damaged site and induction of de novo neurogenesis to replace dead neurons. Aim of the project. We therefore asked whether Rai was expressed in the adult neural stem cells and whether it could have a role in adult neurogenesis. Results. Taking advantage of wild type and Rai-/- mice, we isolated adult neural stem cells from the subventricular zone of the brain and cultured them as neurospheres. We found that Rai is expressed in adult neural stem cells and progenitors, and that a lack of Rai proteins results in an impaired differentiation, with a lower number of neurons, which are also less mature. The absence of Rai also causes an impaired NSC/progenitor migration. The investigation of the signalling mechanisms responsible for these phenotypes revealed that in Rai-/- neurospheres there is a defect in the Wnt/β-catenin pathway activation. We observed that in the absence of Rai casein kinase I activity is enhahanced and β-catenin is hyperphosphorylated, resulting in β-catenin failure to enter the nucleus and activate the transcription of target genes specifically involved in neurogenesis. With this work we describe for the first time a role for Rai in adult neurogenesis through activation of the Wnt/β-catenin pathway. Rai proved to favour both neuronal differentiation and migration of NSC/progenitors, two essential components of neurogenesis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available