The pituitary gland is the major endocrine gland in the forebrain. The hormones secreted from this gland regulate vital processes such as reproduction, growth and stress response. Distinct endocrine cells arise from pituitary precursors cells. The endocrine cells are spatially organized along the anterior-posterior axis within the anterior lobe of the pituitary, the adenohypophysis. Several signaling molecules have been shown to play roles in the development of this endocrine gland. Previous work in our lab showed that Sonic Hedgehog (Shh) is required for induction and patterning of the adenohypophysis. Hedgehog (Hh) signaling is involved in many developmental processes including induction, patterning and differentiation of many tissues. In addition, independent studies show that Fibroblast growth factor (Fgf) signaling also plays a role in the development of zebrafish adenohypophysis. ^ One of the main aims of my dissertation was to determine how the Hh and Fgf signaling pathways specify the functional patterning of the adenohypophysis. Using small molecule inhibitors I show that high levels of Hh signaling are required for the formation of the anterior adenohypophysis, the pars distalis (PD) and high levels of Fgf signaling are required for the formation of the posterior adenohypophysis, the pars intermedia (PI). My dissertation work also shows that high Hh levels are required for differentiation of the endocrine cells in the PD, and in contrast high Fgf levels are required for differentiation of the endocrine cells in the PI. Using live-imaging of a transgenic zebrafish line, I show that the PD and PI originate from distinct regions. My analyses has revealed that graded Hh and Fgf signaling help pattern the adenohypophysis along anterior-posterior axis by guiding endocrine cell differentiation in a dose dependent manner. ^ A related aim of my research was to analyze the role of Hh signaling in zebrafish neural tube patterning. The transcriptional response to varying Hh levels is well characterized in chick and mouse neural tube, and this transcriptional response has been partially described in zebrafish. The analysis of the Hh transcriptional response in wild type, Hh mutant and Hh over-expressing embryos show that there is a conserved transcriptional response to Hh signaling in the zebrafish neural tube. My comprehensive analyses of the Hh transcriptional response in the zebrafish neural tube provides a useful tool for the characterization of Hh signaling in zebrafish. ^
| Identifer | oai:union.ndltd.org:UMASS/oai:scholarworks.umass.edu:dissertations-6426 |
| Date | 01 January 2008 |
| Creators | Guner, Burcu |
| Publisher | ScholarWorks@UMass Amherst |
| Source Sets | University of Massachusetts, Amherst |
| Language | English |
| Detected Language | English |
| Type | text |
| Source | Doctoral Dissertations Available from Proquest |
Page generated in 0.0016 seconds