The long-term objective of this research project is to understand the cellular events that regulate progenitor cells and neurogenesis. This study will use genetic approaches to understand the signaling mechanisms that regulate the cell fate decisions in the development of the diverse cell-types of the olfactory epithelium. The olfactory epithelium is a sensory epithelium that constantly renews neurons from progenitor cells and can regenerate upon injury. The development of the olfactory epithelium involves the establishment and maintenance of progenitor cells, neurogenesis of olfactory receptor neurons, and formation of support cells called sustentacular cells. However, the regulation of these cell-fate decisions is not understood. The simple, well-defined architecture and the availability of cell-type and differentiation-state specific markers make the olfactory epithelium an excellent model for studying the processes of neurogenesis and progenitor cell regulation. There is evidence that Bone Morphogenetic Protein (BMP) signaling is involved in olfactory epithelial development. This study will first define which BMP signaling components are present in specific cell types of the olfactory epithelium, and secondly, activation of BMP signaling will be assessed. Subsequently, genetic loss-of-function mutants in specific BMP signaling components will be investigated to determine how specific BMP signaling regulates progenitor maintenance and neurogenesis. This will involve analyzing mutants for changes in a range of cell-type and differentiation-state specific markers, cell proliferation, and cell death. Ultimately this study should provide insight into how BMP signaling regulates these processes, and it will lay the foundation for future studies on signaling pathway interactions and the regulation of regeneration. The olfactory epithelium contains thousands of neurons that sense volatile chemicals in the environment, and it renews these neurons throughout life and can regenerate upon injury. However, the molecular and cellular mechanisms that regulate the establishment of this tissue are poorly understood. Understanding how a regenerative tissue is established at the molecular and cellular level has great promise for gaining insights into how to deal with damage and disease of neural tissue.
| Fletcher, Russell B; Prasol, Melanie S; Estrada, Jose et al. (2011) p63 regulates olfactory stem cell self-renewal and differentiation. Neuron 72:748-59 |
