| During development, the growing embryo maintains a balance between differentiation and proliferation within stem cells and progenitor cells in order to produce the characteristic size, shape, and complement of cell types typical of the mature organism. However, these cells do not exist in a static environment during development; instead the actions of multiple intrinsic and extrinsic factors continually act to shift this equilibrium toward a differentiated or undifferentiated state. This dissertation addresses these signals that propel a cell to adopt a differentiated state or promote its progression through the cell cycle, maintaining a population of undifferentiated precursors.; Specifically, I investigated helix-loop-helix transcription factors during olfactory development in Xenopus. I show that basic HLH (bHLH) and repeat HLH (rHLH) transcription factors are sequentially expressed during olfactory placode development. Furthermore, I demonstrate that overexpression of the intrinsic bHLH transcription factor, Xath5, pushes precursors cells towards a differentiated state, increasing the number of mature olfactory receptor neurons.; I next addressed how extrinsic signals might influence the state of a progenitor cell. I focused this question on the role of Wnt/Frizzled signaling during early eye and neuroendocrine development. Our work demonstrates that the Frizzled 5 receptor is expressed in the developing mouse retina and pituitary. I show that, in the retina and anterior hypothalamus, the loss of this gene affects proliferation and survival of neuronal progenitor cells. I also used a canonical Wnt/beta-catenin mouse reporter line to demonstrate when canonical signaling is active during the development of these tissues and found that at early developmental stages, canonical signaling does not overlap with the regions that express Fz5. I crossed these two lines of mice and demonstrate that the loss of Frizzled 5 activity does not impact canonical Wnt/Frizzled signaling in the retina or neuroendocrine axis, suggesting that this receptor may act through one of the alternative Wnt pathways to exert its influence on retina and neuroendocrine development.; Collectively, my results further my understanding of the impact that intrinsic and extrinsic signaling sources have on progenitor cell proliferation and differentiation. |
