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The role of GDF7 in olfactory epithelium development and regeneration

Posted on:2008-02-08Degree:Ph.DType:Dissertation
University:University of California, IrvineCandidate:Crocker, Candice ElizabethFull Text:PDF
GTID:1444390005966678Subject:Biology
Abstract/Summary:
Neurogenesis, the process by which new neurons are made is ongoing throughout development and postnatal life in vertebrate olfactory epithelium (OE). The continued renewal of olfactory receptor neurons (ORNs) suggests that there are signals integral to the olfactory mucosa that support proliferation and survival of both progenitor and stem cells. Previous work determined that factors made by the stroma underlying the OE promote OE neurogenesis. This effect of stromal factors could be antagonized by a secreted extracellular antagonist of bone morphogenetic proteins, noggin. A candidate approach, in which TGF-beta superfamily members were screened for pro-neurogenic effects, led to the identification of growth and differentiation factor 7 (GDF7) as a neurogenesis-promoting signal in OE development. This manuscript provides evidence from experiments performed in vitro and in vivo that demonstrate a role for GDF7 in the regulation of OE neurogenesis during development. Additionally, preliminary evidence is presented to suggest that Gdf7 plays a role in regenerative neurogenesis following ORN death in the adult mice. Since the presence of stroma-derived GDF7 appears to be crucial for OE neurogenesis, these findings contribute to our understanding of the role of signals, made by the stroma underlying the OE, in the development and maintenance of the OE stem cell niche.; In an environment with limited room for growth but a constant need for neuronal replacement, tight controls on neuron production and survival are essential. Previous work has shown factors such as GDF11 and BMP4 can act to limit progenitor cell numbers in the OE. GDF7, in contrast, acts to increase stem and progenitor cell numbers during development and in the adult OE and may be an important factor involved in the neural regenerative response following OE injury.
Keywords/Search Tags:GDF7, Development, Olfactory, OE neurogenesis, Role
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