title: Partial depletion of yolk during zebrafish embryogenesis changes the dynamics of methionine cycle and metabolic genes.
abstract: BACKGROUND
  Limited nutrient availability during development is associated with metabolic diseases in adulthood. The molecular cause for these defects is unclear. Here, we investigate if transcriptional changes caused by developmental malnutrition reveal an early response that can be linked to metabolism and metabolic diseases.
  
  
  RESULTS
  We limited nutrient availability by removing yolk from zebrafish (Danio rerio) embryos. We then measured genome expression after 8, 24, 32 h post-fertilization (hpf) by RNA sequencing and 48 hpf by microarray profiling. We assessed the functional impact of deregulated genes by enrichment analysis of gene ontologies, pathways and CpG sites around the transcription start sites. Nutrient depletion during embryogenesis does not affect viability, but induces a bias towards female development. It induces subtle expression changes of metabolic genes: lipid transport, oxidative signaling, and glycolysis are affected during earlier stages, and hormonal signaling at 48 hpf. Co-citation analysis indicates association of deregulated genes to the metabolic syndrome, a known outcome of early-life nutrient depletion. Notably, deregulated methionine cycle genes indicate altered methyl donor availability. We find that the regulation of deregulated genes may be less dependent on methyl donor availability.
  
  
  CONCLUSIONS
  The systemic response to reduced nutrient availability in zebrafish embryos affects metabolic pathways and can be linked to metabolic diseases. Further exploration of the reported zebrafish model system may elucidate the consequences of reduced nutrient availability during embryogenesis.
authors.affiliation: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. zifei329@hotmail.com.
authors.forename: Yunxian
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. linsen@picb.ac.cn.
authors.forename: Sam E V
authors.initials: SE
authors.lastname: Linsen
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism*; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D006019:Glycolysis / Q000235:genetics; D008715:Methionine / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics; D012313:RNA / Q000032:analysis / Q000302:isolation & purification; D017423:Sequence Analysis, RNA; D015398:Signal Transduction / Q000235:genetics; D015017:Yolk Sac / Q000002:abnormalities*; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D001053:Apolipoproteins; D029961:Zebrafish Proteins; D012313:RNA; D008715:Methionine