| Fatty acids are involved in a diverse range of cellular processes such as energy production, membrane synthesis, intracellular signaling, protein modification and regulation of transcription. In Chapter 1, I demonstrate a method to assay early zebrafish fatty acid metabolism. The approach reveals differences and in fatty acid metabolism over the course of development and differential acyl chain incorporation into complex lipids. Fatty acid activation, an essential step in fatty acid metabolism is catalyzed by a group of enzymes called acyl-CoA synthetases (ACS). In Chapter 2, I identify nine long-chain ACS (acsl) and nine very long-chain ACS (slc27a, Acsvl/Fatp) genes in the zebrafish. There is considerable diversity in the zebrafish ACS gene families that may reflect the importance of specific metabolic events in zebrafish physiology and development. This is clearly demonstrated in Chapters 3 and 4 where antisense targeting of ACSs results in specific developmental defects. In Chapter 3, I show that Acsl4a, a long-chain polyunsaturated fatty acid activating enzyme, is essential for proper patterning of the zebrafish dorsoventral axis. In Chapter 4, I show that disruption of Acsvl1a/Fatp2a and AcsvI1b/Fatp2b results in a defect in primitive erythropoiesis (red blood cell development). Together these results indicate the clear importance of fatty acid metabolism in vertebrate development. |
