Dynamics and Regulation of Olfactory Progenitors during Epithelial Development and Maintenance
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Date
2014-03-28
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Johns Hopkins University
Abstract
In mammals, the olfactory epithelium (OE) is one of the few known sites where neurons are continually made throughout the lifetime of the animal. An in-depth understanding of the mechanisms that facilitate this process could lead to important breakthroughs in the treatment of neurological and psychiatric diseases. At present, neither the identity of the stem cell responsible for this neurogenic capacity nor the mechanisms that lead to their activation is completely understood. In this thesis, I employ novel strategies to conditionally interfere with TGFβ signaling, a known modulator of neurogenesis during development, allowing this pathway to be inhibited in the adult OE for the first time. We show that expressing high levels of the TGFβ inhibitor follistatin does not appear to alter neurogenesis in the adult OE. I concurrently utilized a genetic fate-mapping strategy to examine the dynamics of Mash1-expressing cells. We found that labeling of Mash1-expressing cells postnatally marked a population of transient amplifying cells that produces predominantly neurons. Unilateral lesioning of postnatally-labeled mice leads to the extinction of labeled cells on the lesioned side. In contrast, when labeled in utero, Mash1-expressing cells give rise to a variety of cell types that resemble sustentacular and horizontal basal cells. Together, these experiments support the hypothesis that the mechanisms involved in regulating development of the OE may be distinct from those that maintain it thoroughout life.
Thesis advisor: Randall R. Reed, Ph.D
Thesis reader: Akira Sawa, M.D., Ph.D
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Keywords
olfactory, neurogenesis