Posterior-anterior gradient of zebrafish hes6 expression in the presomitic mesoderm is established by the combinatorial functions of the downstream enhancer and 3'UTR

Kawamura, A., Ovara, H., Ooka, Y., Kinoshita, H., Hoshikawa, M., Nakajo, K., Yokota, D., Fujino, Y., Higashijima, S.I., Takada, S., Yamasu, K.
Developmental Biology   409(2): 543-54 (Journal)
Registered Authors
Higashijima, Shin-ichi, Kawamura, Akinori, Takada, Shinji, Yamasu, Kyo
3′UTR, Expression gradient, Somite, Transcriptional regulation, Zebrafish, hairy-related gene
MeSH Terms
  • 3' Untranslated Regions/genetics*
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors/genetics*
  • Basic Helix-Loop-Helix Transcription Factors/metabolism
  • Binding Sites
  • Body Patterning/genetics
  • Embryo, Nonmammalian/metabolism
  • Enhancer Elements, Genetic/genetics*
  • Fibroblast Growth Factors/pharmacology
  • Gene Expression Regulation, Developmental/drug effects
  • Genes, Reporter
  • Green Fluorescent Proteins/metabolism
  • Mesoderm/drug effects
  • Mesoderm/embryology*
  • Mesoderm/metabolism
  • Molecular Sequence Data
  • Protein Binding/drug effects
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Repressor Proteins/genetics*
  • Repressor Proteins/metabolism
  • Signal Transduction/drug effects
  • Signal Transduction/genetics
  • Somites/drug effects
  • Somites/embryology*
  • Somites/metabolism
  • Tail/embryology
  • Tretinoin/pharmacology
  • Zebrafish/embryology*
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
26596999 Full text @ Dev. Biol.
In vertebrates, the periodic formation of somites from the presomitic mesoderm (PSM) is driven by the molecular oscillator known as the segmentation clock. The hairy-related gene, hes6/her13.2, functions as a hub by dimerizing with other oscillators of the segmentation clock in zebrafish embryos. Although hes6 exhibits a posterior-anterior expression gradient in the posterior PSM with a peak at the tailbud, the detailed mechanisms underlying this unique expression pattern have not yet been clarified. By establishing several transgenic lines, we found that the transcriptional regulatory region downstream of hes6 in combination with the hes6 3'UTR recapitulates the endogenous gradient of hes6 expression. This downstream region, which we termed the PT enhancer, possessed several putative binding sites for the T-box and Ets transcription factors that were required for the regulatory activity. For example, the T-box transcription factor (Tbx16) and Ets transcription factor (Pea3) bound specifically to the putative binding sites and regulated the enhancer activity in zebrafish embryos. In addition, the 3'UTR of hes6 is required for recapitulation of the endogenous expression. Furthermore, the PT enhancer with the 3'UTR of hes6 responded to the inhibition of retinoic acid synthesis and fibroblast growth factor signaling in a manner similar to endogenous hes6. The results showed that transcriptional regulation by the T-box and Ets transcription factors, combined with the mRNA stability given by the 3'UTR, is responsible for the unique expression gradient of hes6 in the posterior PSM of zebrafish embryos.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes