The Role Of Jagged1 In The Subventricular Zone During Late Embryonic Development
Notch signaling plays an important role in regulating olfactory neurogenesis during development of the mammalian subventricular zone. During development, the Notch signaling pathway is critical for maintenance of neuronal precursors, cell survival, and for neural stem/progenitor cell self-renewal. Notch receptors have been shown to be expressed among the heterogeneous populations of cells in the subventricular zone. However, the regulation of Notch remains poorly understood. In the subventricular zone, the Notch activator Jagged1 has been shown to be expressed in cells adjacent to those expressing Notch receptors. Moreover, a previous study showed that Jagged1 is important for self-renewal of neural stem cells in the subventricular zone during postnatal stages. We utilized a conditional Jagged1 knockout mouse to study the role of Jagged1 in the embryonic subventricular zone. We found that Jagged1 is critical for olfactory neurogenesis during development. Jagged1 mutants exhibited a decrease in the production of neuronal precursors and olfactory interneurons. Additionally, we observed that the loss of Jagged1 increases cell death in the rostral migratory stream, a specialized migratory stream connecting the subventricular zone and the olfactory bulb. Finally, we show that Jagged1 is expressed on neural stem cells. Based on these findings, Jagged1 is proposed as a critical regulator of neurogenesis in the embryonic subventricular zone.
JAGGED1; NEUROGENESIS; embryonic subventricular zone
Lin, David M.
Nowak, Linda M; Collins, Ruth N.; Oswald, Robert Edward
Ph. D., Pharmacology
Doctor of Philosophy
dissertation or thesis