Nature vs. Nurture: Neuronal Diversification in the Olfactory Epithelium.
Abstract: Stem cells
in the olfactory epithelium (OE) can completely regenerate the entire olfactory
neuroepithelium in adult animals, representing a unique, robust system of adult
neurogenesis. These stem cells are classified into two populations: multipotent
horizontal basal cells (HBCMPPs) - the quiescent, reserve stem population, and globose
basal cells (GBCs) - the actively proliferating... read morestem population. GBCs can be
sub-classified into stages of progenitor capacity and neuronal commitment from
multipotent progenitors (GBCMPPs) to immediate neuronal precursors (GBCINPs). During the
transition from a GBCINP to a mature olfactory sensory neuron (OSN), each neuron selects
a single olfactory receptor (OR) allele for expression, out of over 1000 different OR
genes. Despite our knowledge of the basic cell-stage progression during neuronal
maturation in the OE, little is known about stem cell plasticity in respect to the
process of OSN diversification and OR gene selection. In this thesis work, through a
series of transplantation experiments, I found that GBC progenitors are spatially
plastic in respect to both olfactory receptors (ORs) and two regionally expressed
neuronal markers, NADPH:quinone oxidoreductase (NQO1) and olfactory cell adhesion
molecule (OCAM). These data demonstrate that spatial cues influence neuronal
diversification in the OE. To further describe OSN diversification, I characterized the
effect of cell-stage specific loss of lysine specific demethylase 1 (LSD1). LSD1 is a
prime candidate for OR gene regulation as it demethylates at both histone 3, lysine 4
(H3K4) and histone 3, lysine 9 (H3K9), each of which are found on the actively
transcribed OR allele or the silenced OR alleles, respectively. I found that LSD1 is
required for neuronal maturation during a distinct time window between activating
HBCMPPs and GBCINPs . Taken together, this thesis work clarifies the processes of
neuronal maturation and diversification in the olfactory epithelium and advances our
understanding of LSD1-dependent neuronal maturation and stem cell plasticity within the
Thesis (Ph.D.)--Tufts University, 2016.
Submitted to the Dept. of Neuroscience.
Advisor: James Schwob.
Committee: Grace Gill, Brent Cochran, Alan Kopin, and Robert Lane.
Keyword: Neurosciences.read less