Mechanisms of Olfactory Stimulation-dependent Regulation of Neurogenesis
[Thesis]
Bhuiya, Md Ashraful Islam
Santoro, Stephen
University of Wyoming
2020
136 p.
M.S.
University of Wyoming
2020
In mammals, olfactory sensory neurons (OSNs) are born throughout life. Prior to maturation, each newborn OSN chooses to express, out of hundreds of possibilities, a single olfactory receptor (OR), which defines the mature OSN's type. Our group's recent work has demonstrated that a small subset of OSN types in the mouse olfactory epithelium (OE) undergoes neurogenesis in a stimulation-dependent manner. To elucidate the mechanism and function of this phenomenon, one important question is how this type of plasticity changes as a function of an individual's age and environment. To begin to address this question, we quantitatively compared the effects of olfactory deprivation on the abundance of newborn OSNs of multiple types at two different ages (Chapter 2). These experiments revealed that the extent to which different OSN types show stimulation-dependent neurogenesis varies dynamically with an animal's age and/or environment and provided potential clues as to the nature of the stimulating odors. The finding that olfactory stimulation can selectively alter the neurogenesis of specific OSN types was surprising because the relative neurogenesis rates of distinct OSN types are supposedly constant, as they are evidently determined by a process in which each OR is chosen randomly and with a fixed probability. To explain our findings, we have formulated a model in which OR choice occurs in OSN stem cells, a developmental stage considerably earlier than is currently assumed, and that stimulated mature OSNs send feedback signals to promote the selective proliferation of stem cells that are predisposed to the same OR fate. This model predicts that all OSNs derived from a single stem cell should express the same OR. Using a fate-mapping approach, we have taken preliminary steps to test this prediction (Chapter 3). The model further predicts that mature OSNs of types that undergo stimulation-dependent neurogenesis selectively express genes that mediate feedback signaling to stem cells and upregulate their proliferation. Using a single-cell RNA-seq approach to test this prediction, we have identified a set of candidate genes that are selectively expressed in OSNs of types that undergo stimulation-dependent neurogenesis (Chapter 4). Taken together, findings presented in this thesis provide preliminary support for the proposed model. This work is expected to enhance our understanding of olfactory system development and plasticity.