| Notch signaling is required for numerous developmental processes and generates a variety of different cellular responses. It is a core component of the zebrafish somitogenesis oscillator (or clock) that governs the formation of somites, early transient segments that pattern and subdivide the vertebrate trunk. The oscillator generates synchronized oscillations in gene expression that provide the spatiotemporal information required for regular somite formation. Notch signaling is also required for zebrafish midline development, where it mediates cell fate decisions by promoting hypochord cell fates over notochord. The studies in this thesis show that three Notch ligands deltaC tv1, deltaCtv2, and deltaD all send distinct signals during these two developmental processes. Specifically, deltaCtv2 does not signal effectively during somitogenesis while deltaCtv1 and deltaD have unique functions within the somite clock. High resolution in situ hybridization and confocal microscopy studies show that deltaD provides the basal Notch activation required to drive oscillations, while deltaCtv1 produces cyclical pulses of activation that synchronize oscillations between neighboring cells. However, during midline formation, deltaCtv1 shows a very limited ability to signal. deltaCtv2 and deltaD, on the other hand, effectively promote notochord to hypochord transitions with a bias for the anterior or posterior trunk, respectively. Chimeric analysis of these ligands indicate that different signaling capacities in both processes are encoded by the intracellular and extracellular domains, suggesting various combinations of ligand modifications (i.e. ubiquitination, protein-protein interactions) may create unique signaling potentials. Finally, preliminary analysis of a spatiotemporal transgenic system indicates that the FGF and Wnt pathways may also be involved in the zebrafish somite oscillator. |
