Vitamin E is necessary for zebrafish nervous system development

Sci Rep. 2020 Sep 21;10(1):15028. doi: 10.1038/s41598-020-71760-x.


Vitamin E (VitE) deficiency results in embryonic lethality. Knockdown of the gene ttpa encoding for the VitE regulatory protein [α-tocopherol transfer protein (α-TTP)] in zebrafish embryos causes death within 24 h post-fertilization (hpf). To test the hypothesis that VitE, not just α-TTP, is necessary for nervous system development, adult 5D strain zebrafish, fed either VitE sufficient (E+) or deficient (E-) diets, were spawned to obtain E+ and E- embryos, which were subjected to RNA in situ hybridization and RT-qPCR. Ttpa was expressed ubiquitously in embryos up to 12 hpf. Early gastrulation (6 hpf) assessed by goosecoid expression was unaffected by VitE status. By 24 hpf, embryos expressed ttpa in brain ventricle borders, which showed abnormal closure in E- embryos. They also displayed disrupted patterns of paired box 2a (pax2a) and SRY-box transcription factor 10 (sox10) expression in the midbrain-hindbrain boundary, spinal cord and dorsal root ganglia. In E- embryos, the collagen sheath notochord markers (col2a1a and col9a2) appeared bent. Severe developmental errors in E- embryos were characterized by improper nervous system patterning of the usually carefully programmed transcriptional signals. Histological analysis also showed developmental defects in the formation of the fore-, mid- and hindbrain and somites of E- embryos at 24 hpf. Ttpa expression profile was not altered by the VitE status demonstrating that VitE itself, and not ttpa, is required for development of the brain and peripheral nervous system in this vertebrate embryo model.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain / embryology
  • Carrier Proteins / genetics
  • Embryo, Nonmammalian / abnormalities*
  • Embryo, Nonmammalian / drug effects
  • Embryo, Nonmammalian / innervation
  • Gastrulation / drug effects
  • Gastrulation / genetics
  • Gene Expression Regulation, Developmental / drug effects
  • Nervous System / embryology*
  • PAX2 Transcription Factor / genetics
  • SOXE Transcription Factors / genetics
  • Vitamin E / pharmacology
  • Vitamin E / physiology*
  • Vitamin E Deficiency / embryology
  • Zebrafish / embryology*
  • Zebrafish Proteins / genetics*


  • Carrier Proteins
  • PAX2 Transcription Factor
  • SOXE Transcription Factors
  • Zebrafish Proteins
  • alpha-tocopherol transfer protein
  • pax2a protein, zebrafish
  • sox10 protein, zebrafish
  • Vitamin E