The role of RBF in developmentally regulated cell proliferation in the eye disc and in Cyclin D/Cdk4 induced cellular growth

Development. 2002 Mar;129(6):1345-56. doi: 10.1242/dev.129.6.1345.

Abstract

During Drosophila eye development, cell proliferation is coordinated with differentiation. Immediately posterior to the morphogenetic furrow, cells enter a synchronous round of S phase called second mitotic wave. We have examined the role of RBF, the Drosophila RB family homolog, in cell cycle progression in the second mitotic wave. RBF-280, a mutant form of RBF that has four putative cdk phosphorylation sites mutated, can no longer be regulated by Cyclin D or Cyclin E. Expression of RBF-280 in the developing eye revealed that RBF-280 does not inhibit G1/S transition in the second mitotic wave, rather it delays the completion of S phase and leads to abnormal eye development. These observations suggest that RB/E2F control the rate of S-phase progression instead of G1/S transition in the second mitotic wave. Characterization of the role of RBF in Cyclin D/Cdk4-mediated cellular growth showed that RBF-280 blocks Cyclin D/Cdk4 induced cellular growth in the proliferating wing disc cells but not in the non-dividing eye disc cells. By contrast, RBF-280 does not block activated Ras-induced cellular growth. These results suggest that the ability of Cyclin D/Cdk4 to drive growth in the proliferating wing cells is distinct from that in the none-dividing eye cells or the ability of activated Ras to induce growth, and that RBF may have a role in regulating growth in the proliferating wing discs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Cycle / physiology*
  • Cyclin D
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases / physiology*
  • Cyclins / physiology*
  • Drosophila / embryology*
  • Drosophila / physiology*
  • Drosophila Proteins*
  • Eye / cytology
  • Eye / embryology
  • Gene Expression Regulation, Developmental*
  • Mutation
  • Phosphorylation
  • Proto-Oncogene Proteins*
  • Retinoblastoma Protein
  • Transcription Factors / physiology*

Substances

  • CycD protein, Drosophila
  • Cyclin D
  • Cyclins
  • Drosophila Proteins
  • Proto-Oncogene Proteins
  • Rbf protein, Drosophila
  • Retinoblastoma Protein
  • Transcription Factors
  • Cdk4 protein, Drosophila
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases