Zebrafish foxc1a plays a crucial role in early somitogenesis by restricting the expression of aldh1a2 directly

Li, J., Yue, Y., Dong, X., Jia, W., Li, K., Liang, D., Dong, Z., Wang, X., Nan, X., Zhang, Q., Zhao, Q.
The Journal of biological chemistry   290(16): 10216-28 (Journal)
Registered Authors
Liang, Dong, Zhao, Qingshun
MyoD, aldh1a2, deltaC, fibroblast growth factor (FGF), foxc1a, paraxial mesoderm, retinoic acid, somitogenesis, transcription activator-like effector nuclease (TALEN), zebrafish
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Body Patterning/genetics*
  • Embryo, Nonmammalian
  • Fibroblast Growth Factors/antagonists & inhibitors
  • Fibroblast Growth Factors/genetics
  • Fibroblast Growth Factors/metabolism
  • Forkhead Transcription Factors/genetics*
  • Forkhead Transcription Factors/metabolism
  • Gene Expression Regulation, Developmental*
  • Intracellular Signaling Peptides and Proteins/genetics
  • Intracellular Signaling Peptides and Proteins/metabolism
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism
  • MyoD Protein/genetics
  • MyoD Protein/metabolism
  • Promoter Regions, Genetic
  • Receptors, Notch/genetics
  • Receptors, Notch/metabolism
  • Retinal Dehydrogenase/genetics*
  • Retinal Dehydrogenase/metabolism
  • Signal Transduction
  • Somites/growth & development
  • Somites/metabolism*
  • Tretinoin/metabolism
  • Zebrafish/genetics*
  • Zebrafish/growth & development
  • Zebrafish/metabolism
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
25724646 Full text @ J. Biol. Chem.
Foxc1a is a member of forkhead transcription factors. It plays an essential role in zebrafish somitogenesis. However, little is known about the molecular mechanisms underlying its controlling somitogenesis. To uncover how foxc1a regulates zebrafish somitogenesis, we generated foxc1a knock out zebrafish using TALEN (transcription activator-like effector nuclease) technology. The foxc1a null embryos exhibited defective somites at early development. Analyses on the expressions of the key genes that control processes of somitogenesis revealed that foxc1a controlled early somitogenesis by regulating the expression of myod1. In the somites of foxc1a knockout embryos, expressions of fgf8a and deltaC were abolished whereas aldh1a2 (responsible for providing retinoic acid (RA) signaling) was significantly increased its expression. Once the increased RA level in the foxc1a null embryos was reduced by knocking down aldh1a2, the reduced expression of myod1 was partially rescued by resuming expressions of fgf8a and deltaC in the somites of the mutant embryos. Moreover, chromatin immuoprecipitation assay on zebrafish embryos revealed that Foxc1a bound aldh1a2 promoter directly. On the other hand, neither knocking down fgf8a nor inhibiting Notch signaling affected the expression of aldh1a2 though knocking down fgf8a reduced expression of deltaC in the somites of zebrafish embryos at early somitogenesis and vice versa. Taken together, our results demonstrate that foxc1a plays an essential role in early somitogenesis by controlling Fgf and Notch signaling through restricting the expression of aldh1a2 in paraxial mesoderm directly.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes