| Description |
The occurrence of postembryonic neurogenesis in the vertebrate brain is now a widely accepted belief. Observations of adult neurogenesis have been made in multiple regions of the brain across numerous species. However, why some regions continue to make neurons while others do not is not completely clear. The functional significance of continual neurogenesis is also not well understood and remains a highly investigated topic. Determining why the brain continues to make new neurons under normal physiologic and pathophysiologic conditions will allow us to better understand how it functions overall. Additionally, a greater understanding of postembryonic neurogenesis will provide valuable therapeutic benefits to human life in terms of treating brain injury and neurodegenerative disease. One of the more recently identified regions to undergo continual neurogenesis is the hypothalamus-the homeostatic control center of the brain. It responds to both physiological and external environmental cues in order to regulate conditions in the body, such as body temperature, heart rate, sleep/wake cycles, and energy balance. Previous studies in Dr. Richard Dorsky's lab identified a population of neural precursors that express dlx transcription factors and continue to generate new neurons throughout adulthood in the hypothalamus of zebrafish. When I began my studies in this lab, I wanted to iv understand the functional significance of continual neurogenesis of this cell population. In this dissertation, I present findings that further our understanding of the factors regulating postembryonic neurogenesis of these neural precursors and the functional role these cells play. I developed reagents that aided in determining that the dlx+ cells were regulated by Wnt signaling. I also developed reagents that lead to the identification and characterization of a neurogenic radial glia-like population of cells, called tanycytes, residing in the caudal hypothalamus, which our lab went on to show was a stem cell population capable of giving rise to many cell types postembryonically. Furthermore, I determined that the dlx+ neural precursors generated tyrosine hydroxylase 2 (th2)-positive dopaminergic neurons that modulate swimming behavior. Finally, I went on to show that these th2+ neurons are capable of functional recovery. This discovery has potential therapeutic significance in future studies of neurodegenerative disease, such as Parkinson's disease. Overall, my investigations have lead to significant advances in our understanding of postembryonic neurogenesis. |
