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

  • Cell Rep. 2026 May 26;45(5):117295. doi: 10.1016/j.celrep.2026.117295.
Tong Sun  1 ,  Yizhu Tao  1 ,  Yingjie Zeng  1 ,  Ran Ai  1 ,  Tong Li  1 ,  Xinyu Li  1 ,  Xueshan Li  1 ,  Ruiping He  1 ,  Zhikun Jia  1 ,  Xiaohan Sun  2 ,  Zhuanghui Feng  1 ,  Xiangyi Liu  1 ,  Xingyu Kong  3 ,  Linzhang Huang  1 ,  Lei Chen  4 ,  Jinfei Ni  5 ,  Li Chen  6 ,  Wei Dai  7
Affiliations
  • 1. State Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China.
  • 2. Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institute of Pediatrics, National Children's Medical Center, Children's Hospital, Fudan University, Shanghai, China.
  • 3. State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Fudan University, Shanghai, China.
  • 4. Renji Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 5. Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institute of Pediatrics, National Children's Medical Center, Children's Hospital, Fudan University, Shanghai, China. Electronic address: [email protected].
  • 6. Renji Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: [email protected].
  • 7. State Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China. Electronic address: [email protected].
PMID: 42018437 DOI: 10.1016/j.celrep.2026.117295
Abstract

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.

Keywords
CP: developmental biology; CP: metabolism; Hnf4; Lipf; Mttp; Pla2g15; cathepsin; embryogenesis; lipid mobilization; lipoprotein transport; maternal nutrient utilization; yolk syncytial layer.
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