Increased yolk lipid mobilization promotes zebrafish post-segmentation growth via an Hnf4-lipoprotein axis

Embryogenesis demands an increasing nutrient supply, yet how maternal reserves are temporally delivered remains unclear. In egg-laying vertebrates, reserves are pre-deposited in the yolk, providing a closed system to dissect this problem. Using zebrafish, we quantified mobilization of the two major yolk stores-protein and lipid-across embryogenesis. Protein catabolism is continuous from cleavage to hatching, whereas bulk lipid release is increased during embryogenesis. This increase is coupled to zygotic activation of hnf4a/b, which promotes a yolk-syncytial lipoprotein assembly/transport. The acidic lipases Pla2g15 and Lipf contribute to yolk-granule lipid hydrolysis, while Mttp-dependent lipoprotein export mediates delivery of yolk-derived lipids to the embryo through the circulation. Inhibiting this lipid-delivery pathway has minimal early effect but impairs post-segmentation growth. Comparative transcriptomic analyses further reveal a similar Hnf4-lipoprotein expression program in the mammalian yolk sac. Together, these findings define a stage-tuned, transcriptionally gated strategy for maternal nutrient utilization during early development.