Ras-Related Nuclear Protein is required for late developmental stages of retinal cells in zebrafish eyes

Lin, C.Y., Huang, H.Y., Lu, P.N., Lin, C.W., Lu, K.M., Tsai, H.J.
The International journal of developmental biology   59: 435-442 (Journal)
Registered Authors
Tsai, Huai-Jen
Ran, zebrafish, retinal cells, eye development
MeSH Terms
  • Adaptor Proteins, Signal Transducing/genetics
  • Adaptor Proteins, Signal Transducing/metabolism*
  • Animals
  • Base Sequence
  • Blotting, Western
  • Cell Differentiation
  • Cell Growth Processes
  • Eye Proteins/genetics
  • Eye Proteins/metabolism*
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Developmental*
  • Immunoenzyme Techniques
  • Immunoprecipitation
  • In Situ Hybridization
  • Molecular Sequence Data
  • Organogenesis/physiology
  • Retina/cytology*
  • Retina/metabolism
  • Zebrafish/growth & development*
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • ran GTP-Binding Protein/genetics
  • ran GTP-Binding Protein/metabolism*
26864484 Full text @ Int. J. Dev. Biol.
Ras-related nuclear protein (Ran) is involved in cell division by regulating nucleocytoplasmic transport and modulating the assembly of tubulin. However, its function in embryonic development is unclear. We used zebrafish to study the roles of Ran in eye development. The ran transcripts were restrictedly expressed in head and eyes after the pharyngula stage. The microphthalmos, in which no ordered layers with differentiated retinal cells were detected, was observed in the ran-deficient embryos. They exhibited faster decline cyclinD1-expressed cells, suggesting that cell cycle regulation in retinae was defective. The apoptotic signals in the retinae of ran-deficient embryos remained low at early (24 hpf) stage. Early eye field specification markers, rx1 and pax6, were only slightly affected, and markers for establishing axon migration, fgf8 and pax2, were normally expressed, suggesting Ran is not required in the early stages of eye development. However, the early optic nerve differentiation marker p57kip2 was not expressed at middle (48 hpf) and late (72 hpf) stages. We also observed a decrease in the retinal neuron proteins HuC and Neurolin. The proneural gene ath5, which first determines the cell fate of the developing ganglion cell layer, was undetectable. Furthermore, we found that Ran was associated with ADP-ribosylation factor-like protein 6-interacting protein 1 (Arl6ip1), which plays a role in retinal development, suggesting that Ran associates with Arl6ip1 to regulate retinal development. Therefore, while the effects of Ran are minimal during early specification of the eye field, Ran is required for proliferation and differentiation of retinal cells at later developmental stages.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes