Zebrafish znfl1s regulate left-right asymmetry patterning through controlling the expression of fgfr1a

Li, J., Gao, F., Zhao, Y., He, L., Huang, Y., Yang, X., Zhou, Y., Yu, L., Zhao, Q., Dong, X.
Journal of Cellular Physiology   234(3): 1987-1995 (Journal)
Registered Authors
Zhao, Qingshun
Nodal-Pitx2 pathway, fgfr1a, foxj1a, left-right (LR) asymmetry, zebrafish, zinc finger transcription factor 1 (znfl1s)
MeSH Terms
  • Animals
  • Body Patterning/genetics*
  • Cilia/genetics
  • Forkhead Transcription Factors/genetics
  • Forkhead Transcription Factors/metabolism
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Organizers, Embryonic/embryology
  • Organizers, Embryonic/metabolism
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Receptor, Fibroblast Growth Factor, Type 1/genetics*
  • Receptor, Fibroblast Growth Factor, Type 1/metabolism
  • Signal Transduction/genetics
  • Transcription Factors/antagonists & inhibitors
  • Transcription Factors/genetics*
  • Transcription Factors/metabolism
  • Zebrafish/embryology*
  • Zebrafish/genetics*
  • Zebrafish/metabolism
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
30317609 Full text @ J. Cell. Physiol.
Proper left-right (LR) axis establishment is critical for organogenesis in vertebrates. Previously, we reported that zinc finger transcription factors zinc finger transcription factor 1 (znfl1s) are expressed in the tailbud and axial mesoderm in zebrafish. However, a role of znfl1s in LR axis development has not been demonstrated. Here, we discovered that the knockdown of znfl1s using morpholino (MO) in whole embryos or dorsal forerunner cells (DFCs) interrupted LR asymmetry and normal development of the heart, liver, and pancreas. Whole-embryo knockdown of znfl1s by MO or clustered regularly interspaced short palindromic repeat (CRISPR) interference (CRISPRi) resulted in the absent expression of nodal gene spaw and Nodal signaling-related genes lft1, lft2, and pitx2c in the left lateral plate mesoderm (LPM), and Spaw, Lft1, Lft2, and Pitx2c play important roles in LR axis development in zebrafish. However, specific knockdown of znfl1s in DFCs resulted in random expression of spaw, lft1, lft2, and pitx2c. Knockdown of znfl1s led to abnormal cilia formation by the downregulation of fgfr1a and foxj1a expression. The expression of spaw, lft1, lft2, and pitx2c was partially rescued by the overexpression of fgfr1a mRNA in znfl1s morphants. Taken together, our results suggest that znfl1s regulate laterality development in zebrafish embryos through controlling the expression of fgfr1a.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes