Title

The Subventricular Zone Microenvironment and Its Regulation

Date of Completion

January 2011

Keywords

Biology, Neurobiology

Degree

Ph.D.

Abstract

The subventricular zone (SVZ) is the larger of two neurogenic niches in the murine brain that persists throughout adulthood. Stem cells in the region provide a constant supply of neuronal precursors that migrate through the anterior forebrain to the olfactory bulb where they differentiate and integrate into the olfactory network. This thesis consists of two studies both aimed at elucidating the mechanisms regulating proliferation, migration, and differentiation in the SVZ microenvironment, but through two different approaches. In the first study we utilize a disease model mouse, the MRL/MpJ, which develops late onset systemic lupus erythematosus, but has enhanced regenerative capacities. We revealed these mice had increased SVZ neurogenesis that coincided with clusters of proliferative cells associated with blood vessels. Our study supports the idea that the neural vasculature provides important regulatory signals to the region. In the second study, we focused on EphA4, a tyrosine kinase receptor important for neural development. Its continued expression in the adult SVZ led us to hypothesize that it retained a regulatory role within the region. Using an EphA4 knockout mouse, we reveal that EphA4 organizes astrocytes into glial tubes, which help guide neuroblasts to their destination, the olfactory bulb. These findings provide insight for strategies aimed at promoting neurogenesis and may lead to the development of therapeutic treatments for neurodegenerative diseases. ^

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