Zebrafish yolk phenotype screen reveals four potential genes involved in lipid metabolism

Nhan Le

Mentor: Steve Farber

Supervisor: Maggie Shen

Carnegie Institution for Science - Department of Embryology

Dyslipidemia is a major cause of cardiovascular disease, however not much is known about the underlying mechanisms. The zebrafish is a powerful model for studying human disease, particularly lipid metabolic disorders, due to their transparent larvae, fecundity, and genetic tractability. During the first few days of development, the zebrafish solely relies on its yolk as the source of food. The yolk syncytial layer (YSL) that surrounds the yolk acts as a digestive organ, similar to the intestine and liver, which packages lipids from the yolk into lipoproteins and distributes them throughout the body. An opaque and darkened yolk phenotype has been demonstrated by prior work in the Farber lab as an indicator of altered lipid metabolism. This subtle phenotype is often overlooked in studies not involving lipid metabolism. Here I report the results of a systematic review of the zebrafish literature to identify abnormal yolk phenotypes within published zebrafish images. Using this approach I identified four potential genes, S-adenosylhomocysteine hydrolase (Ahcy), (pro)renin receptor (Atp6ap2), aryl hydrocarbon receptor (Ahr), and Liver X Receptor (Lxr), that may play an essential role in yolk lipid metabolism. These data not only provide the basis for future research on the role of Ahcy, Atp6ap2, Ahr and Lxr in lipoprotein metabolism but support an even bigger screen of published zebrafish images to identify additional genes regulating lipid metabolism.