Co-ordinating retinal histogenesis: early cell cycle exit enhances early cell fate determination in the Xenopus retina

Development. 2002 May;129(10):2435-46.


The laminar arrays of distinct cell types in the vertebrate retina are built by a histogenic process in which cell fate is correlated with birth order. To explore this co-ordination mechanistically, we altered the relative timing of cell cycle exit in the developing Xenopus retina and asked whether this affected the activity of neural determinants. We found that Xath5, a bHLH proneural gene that promotes retinal ganglion cell (RGC) fate, ( Kanekar, S., Perron, M., Dorsky, R., Harris, W. A., Jan, L. Y., Jan, Y. N. and Vetter, M. L. (1997) Neuron 19, 981-994), does not cause these cells to be born prematurely. To drive cells out of the cell cycle early, therefore, we misexpressed the cyclin kinase inhibitor, p27Xic1. We found that early cell cycle exit potentiates the ability of Xath5 to promote RGC fate. Conversely, the cell cycle activator, cyclin E1, which inhibits cell cycle exit, biases Xath5-expressing cells toward later neuronal fates. We found that Notch activation in this system caused cells to exit the cell cycle prematurely, and when it is misexpressed with Xath5, it also potentiates the induction of RGCs. The potentiation is counteracted by co-expression of cyclin E1. These results suggest a model of histogenesis in which the activity of factors that promote early cell cycle exit enhances the activity of factors that promote early cellular fates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Cycle / genetics*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cyclin E / genetics
  • Cyclin E / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27
  • Drosophila Proteins*
  • Embryo, Nonmammalian
  • Eye Proteins / genetics*
  • Eye Proteins / metabolism
  • Female
  • Gene Expression Regulation, Developmental*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neuroglia / cytology
  • Neuroglia / metabolism
  • Neurons / metabolism
  • Receptors, Notch
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Retina / cytology
  • Retina / embryology*
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism
  • Xenopus Proteins*
  • Xenopus laevis / embryology*
  • Xenopus laevis / genetics


  • ATOH7 protein, Xenopus
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Cycle Proteins
  • Cyclin E
  • Drosophila Proteins
  • Eye Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Receptors, Notch
  • Repressor Proteins
  • Su(H) protein, Drosophila
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Xenopus Proteins
  • Xicl protein, Xenopus
  • Cyclin-Dependent Kinase Inhibitor p27
  • NeuroD protein