This item is under embargo and not available online per the author's request. For access information, please visit http://libanswers.wustl.edu/faq/5640.

ORCID

http://orcid.org/0000-0001-7965-2674

Date of Award

Spring 5-15-2020

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Developmental, Regenerative, & Stem Cell Biology)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

The olfactory epithelium (OE) is a neurosensory organ required for the sense of smell. Turbinates, bony projections from the nasal cavity wall, increase the surface area within the nasal cavity lined by the OE. We identified a population of OE progenitor cells that expand horizontally during development to populate all lineages of the mature OE and increase OE surface area. We show that these Fgf20-positive, epithelium-spanning progenitor (FEP) cells are responsive to Wnt/β-Catenin signaling. Wnt signaling suppresses FEP cell differentiation into OE basal progenitors and their progeny, and positively regulates Fgf20 expression. We further show that FGF20 signals to the underlying mesenchyme to regulate the growth of turbinates. By these mechanisms, growth of the OE in surface area is directly linked to the growth of the underlying bone. The cochlea is a neurosensory organ required for hearing. Development of the cochlear sensory epithelium, which contains sensory hair cells (HCs) and supporting cells (SCs) that detect sound, occurs in two main steps: progenitor specification and sensory cell differentiation. FGF20-FGFR1 signaling is necessary for HC and SC development, and the loss of either Fgfr1 or Fgf20 leads to a loss of HCs and SCs in a similar pattern. We show that FGFR1 functions in both steps of cochlear sensory epithelium development, while FGF20 only functions during differentiation, suggesting that another FGF ligand activates FGFR1 during progenitor specification. Interestingly, we also uncovered an epistatic interaction between Fgf20 and Sox2. We further use Translating Ribosome Affinity Purification to detect transcriptomic changes in sensory progenitor cells in the absence of FGF20, and identify many genes downstream of FGF20 potentially important for differentiation.

Language

English (en)

Chair and Committee

David M. Ornitz

Committee Members

Joseph D. Dougherty, Timothy E. Holy, Kristen L. Kroll, Mark E. Warchol,

Available for download on Wednesday, March 23, 2022

Share

COinS