Characterization of factors required for asymmetric organ development in the vertebrate embryo

Vertebrate embryos show stereotyped positioning of organs about the left-right axis. Proper asymmetric development of these tissues requires coordination between establishment of laterality cues and organ-specific patterning. In zebrafish, left-right organ asymmetries are observed within the viscera and the brain. In this dissertation, I characterize multiple players required for asymmetric organ development in zebrafish: Some are required for early left-right patterning, others are required for subsequent organ development, and still others are required for both processes. sec10 and zoolander are required for providing global laterality cues in the developing embryo. Interestingly, they not only function during left-right patterning, but are also important for other developmental processes involving cilia function. My analysis of bmp4 mutants, which fail to show laterality defects, challenges published work arguing that the Bmp4 ligand is required for global left-right patterning. Characterization of Bmp receptor mutants, lost-a-fin, confirms that Bmp signaling plays a role during early left-right patterning, albeit in a Bmp4-independent manner. Unexpectedly, analysis of lost-a-fin mutants reveals an additional requirement for Bmp signaling in the development of asymmetric brain structures. Analysis of the smoothened mutant demonstrates a similar role for Hedgehog signaling in regulating the early laterality and the later development of asymmetric brain structures. Thus, Bmp and Hedgehog signaling are required for both providing laterality cues and for organ development in the brain. By contrast, the brain ventricle formation mutants schnitter and nagie oko demonstrate that brain morphogenesis is not required for early left-right patterning, but is required for the subsequent development of asymmetric structures in the brain. Together, my work highlights the complex contribution of multiple genes---encompassing those important for cilia function, Bmp signaling, Hedgehog signaling, and brain ventricle morphogenesis---in the proper asymmetric development of organs in zebrafish.